Podcasts about endoplasmic reticulum

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Best podcasts about endoplasmic reticulum

Latest podcast episodes about endoplasmic reticulum

Neuro Current: An SfN Journals Podcast
#27 JNeurosci Spotlight: Selective Serotonin Reuptake Inhibitors within Cells: Temporal Resolution in Cytoplasm, Endoplasmic Reticulum, and Membrane

Neuro Current: An SfN Journals Podcast

Play Episode Listen Later Jul 2, 2024 40:31


Aaron Nichols discusses his paper, “Selective Serotonin Reuptake Inhibitors within Cells: Temporal Resolution in Cytoplasm, Endoplasmic Reticulum, and Membrane,” published in Vol. 43, Issue 13 of JNeurosci in 2023, with Megan Sansevere from SfN's Journals' staff. Find the rest of the Spotlight collection here. With special guest: Aaron Nichols Hosted by: Megan Sansevere On Neuro Current, we delve into the stories and conversations surrounding research published in the journals of the Society for Neuroscience. Through its publications, JNeurosci, eNeuro, and the History of Neuroscience in Autobiography, SfN promotes discussion, debate, and reflection on the nature of scientific discovery, to advance the understanding of the brain and the nervous system.  Find out more about SfN and connect with us on X, Instagram, and LinkedIn. 

JACC Speciality Journals
JACC: CardioOncology – Endoplasmic Reticulum Selective Autophagy Alleviates Anthracycline-Induced Cardiotoxicity

JACC Speciality Journals

Play Episode Listen Later Oct 17, 2023 2:58


PaperPlayer biorxiv cell biology
Chaperone Complexes From The Endoplasmic Reticulum (ER) And The Cytosol Inhibit wt-p53 By Activation The ER To Cytosol Signaling.

PaperPlayer biorxiv cell biology

Play Episode Listen Later Aug 3, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551134v1?rss=1 Authors: Dabsan, S., Zur, G., Gilad, A., Igbaria, A. Abstract: The Endoplasmic Reticulum (ER) is an essential sensing organelle responsible for the folding and secretion of almost one-third of eukaryotic cells' total proteins. The ER contains numerous enzymes and chaperones which assist in oxidative protein folding and other posttranslational modifications. However, environmental, chemical, and genetic insults often lead to protein misfolding in the ER, accumulating misfolded proteins, altering homeostasis, and causing ER stress. Recently, we reported a novel ER surveillance mechanism by which proteins from the secretory pathway are refluxed to the cytosol to relieve the ER of its content during stress. In cancer cells, the refluxed proteins gain new pro-survival functions, thereby increasing cancer cell fitness. We termed this phenomenon ER to Cytosol Signaling (or ERCY). In yeast, ERCYS is regulated by HLJ1 (an ER-resident tail-anchored HSP40 cochaperone). Here, we found that in mammalian cells, HLJ1 has five putative orthologs possessing J-domains facing the cytosol. Among those, DNAJB12 and DNAJB14 appear to be the most significant, as they were shown to mediate retrograde trafficking/entry into the cytosol from the ER of nonenveloped viruses in a mechanism similar to ERCYS. Mechanistically, we found that DNAJB12 and DNAJB14 bind the cytosolic HSC70 and its cochaperone SGTA - through their cytosolically localized J-domains to facilitate ER-protein reflux to the cytosol. Moreover, we found that DNAJB12 is necessary and sufficient to drive this phenomenon to increase AGR2 reflux and inhibit wt-p53 during ER stress. Thus, we concluded that targeting the DNAJB12/14-HSC70/SGTA axis is a promising strategy to inhibit ERCYS and impair cancer cell fitness. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Cold temperature induces a TRPM8-independent calcium release from the endoplasmic reticulum in human platelets

PaperPlayer biorxiv cell biology

Play Episode Listen Later Jul 19, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.19.549670v1?rss=1 Authors: Stratiievska, A., Filippova, O., Ozpolat, T., Byrne, D., Bailey, S. L., Mollica, M. Y., Harris, J., Esancy, K., Chen, J., Dhaka, A., Sniadecki, N. J., Lopez, J. A., Stolla, M. Abstract: Platelets are sensitive to temperature changes and akin to sensory neurons, are activated by a decrease in temperature. However, the molecular mechanism of this temperature-sensing ability is unknown. Yet, platelet activation by temperature could contribute to numerous clinical sequelae, most importantly to reduced quality of ex vivo-stored platelets for transfusion. In this interdisciplinary study, we present evidence for the expression of the temperature-sensitive ion channel transient receptor potential cation channel subfamily member 8 (TRPM8) in human platelets and precursor cells. We found the TRPM8 mRNA and protein in MEG-01 cells and platelets. Inhibition of TRPM8 prevented temperature-induced platelet activation and shape change. However, chemical agonists of TRPM8 did not seem to have an acute effect on platelets. When exposing platelets to below-normal body temperature, we detected a cytosolic calcium increase which was independent of TRPM8 but was completely dependent on the calcium release from the endoplasmic reticulum. Because of the high interindividual variability of TRPM8 expression, a population-based approach should be the focus of future studies. Our study suggests that the cold response of platelets is complex and TRPM8 appears to play a role in early temperature-induced activation of platelets, while other mechanisms likely contribute to later stages of temperature-mediated platelet response. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Sommerfeld Theory Colloquium (ASC)
Multispherical shapes, constant-mean-curvature surfaces, and the endoplasmic reticulum

Sommerfeld Theory Colloquium (ASC)

Play Episode Listen Later Jul 12, 2023 64:15


The cells of our body are divided up into separate subcompartments by fluid membranes with a thickness of only a few nanometers. Even though these membranes provide robust barriers for the exchange of molecules between different compartments, they can easily remodel their shape and topology. [1] A particularly interesting example of shape remodeling is the formation of multispherical shapes which represent constant- mean-curvature surfaceswith two values of the mean curvature. [2] The individual spheres are connected by membrane necks which are crucial for topology remodeling by membrane fission and fusion. Multispherical shapes can attain many distinct patterns with multispherical junctions. The latter geometry is reminiscent of the endoplasmic reticulum, a fascinating organelle that forms a large network of membrane nanotubes connected by three-way junctions. [1] R. Lipowsky. Remodeling of Membrane Shape and Topology by Curvature Elasticity and Membrane Tension. Adv. Biology 6, 2101020 (2022) [2] R. Lipowsky. Multispherical shapes of vesicles highlight the curvature elasticityof biomembranes. Adv. Colloid Interface Sci. 301, 102613 (2022)

PaperPlayer biorxiv cell biology
Sse1, Hsp110 chaperone of yeast, controls the cellular fate during Endoplasmic Reticulum-stress

PaperPlayer biorxiv cell biology

Play Episode Listen Later Jun 29, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.29.547006v1?rss=1 Authors: Jha, M. P., Kumar, V., Sharma, L., Ghosh, A., Mapa, K. Abstract: Sse1 is a cytosolic Hsp110 molecular chaperone of yeast, Saccharomyces cerevisiae. Its multifaceted roles in cellular protein homeostasis as Nucleotide Exchange Factor (NEF), as protein-disaggregase and as a Chaperone linked to Protein Synthesis (CLIPS), are well documented. In the currently study, we show that SSE1 genetically interacts with IRE1 and HAC1, the Endoplasmic Reticulum-Unfolded Protein Response (ER-UPR) sensors implicating its role in ER protein homeostasis. Interestingly, absence of this chaperone imparts unusual resistance to tunicamycin-induced ER stress which depends on the intact Ire1-Hac1 mediated ER-UPR signalling. Furthermore, cells lacking SSE1 show ER-stress-responsive inefficient reorganization of translating ribosomes from polysomes to monosomes and increased monosome content that drive uninterrupted protein translation. In consequence, the kinetics of ER-UPR is starkly different in sse1{Delta} strain where we show that stress response induction and restoration of homeostasis is prominently faster in contrast to the wildtype (WT) cells. Importantly, Sse1 plays a critical role in controlling the ER-stress mediated cell division arrest which is escaped in sse1{Delta} strain during chronic tunicamycin stress. Consequently, sse1{Delta} strain shows significantly higher cell viability in comparison to WT yeast, following short-term as well as long-term tunicamycin stress. In summary, we demonstrate a new role of Sse1 in ER protein homeostasis where the chaperone genetically interacts with ER-UPR pathway, controls the protein translation during ER stress and the kinetics of ER-UPR. More importantly, we show the crtiical role of Sse1 in regulating the ER-stress-induced cell division arrest and cell death during global ER stress by tunicamycin. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Hypoxia induced oxidative stress and endoplasmic reticulum stress promoted myocardial cell fibrosis

PaperPlayer biorxiv cell biology

Play Episode Listen Later Jun 26, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.24.546381v1?rss=1 Authors: guang, x., jiang, z., chun, z. Abstract: Myocardial cells, fibroblasts and vascular cells in the heart are connected by a complex matrix mainly composed of fibrillar collagen, which helps to protect the integrity and compliance of the heart structure. Previous studies have shown that hypoxia can induce myocardial hypoxia, but the mechanism is still unclear. In this study, we found that hypoxia promotes TGF beta induced collagen deposition and myocardial fibrosis by inducing Endoplasmic reticulum stress and oxidative stress in cardiomyocytes. Moreover, we also found that antioxidant drugs can effectively alleviate hypoxia induced myocardial fibrosis. Therefore, our study provides an experimental basis for the treatment of myocardial fibrosis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Luminal transport rates through intact endoplasmic reticulum limit the magnitude of localized Ca2+ signals

PaperPlayer biorxiv cell biology

Play Episode Listen Later Jun 26, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.23.546357v1?rss=1 Authors: Crapart, C., Scott, Z. C., Konno, T., Sharma, A., Bailey, D. M., Avezov, E., Koslover, E. F. Abstract: The endoplasmic reticulum (ER) forms an interconnected network of tubules stretching throughout the cell. Understanding how ER functionality relies on its structural organization is crucial for elucidating cellular vulnerability to ER perturbations, which have been implicated in several neuronal pathologies. One of the key functions of the ER is enabling Ca2+ signalling by storing large quantities of this ion and releasing it into the cytoplasm in a spatiotemporally controlled manner. Through a combination of physical modeling and live-cell imaging, we demonstrate that alterations in ER shape significantly impact its ability to support efficient local Ca2+ releases, due to hindered transport of luminal content within the ER. Our model reveals that rapid Ca2+ release necessitates mobile luminal buffer proteins with moderate binding strength, moving through a well-connected network of ER tubules. These findings provide insight into the functional advantages of normal ER architecture, emphasizing its importance as a kinetically efficient intracellular Ca2+ delivery system. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Identification of ERAD-dependent degrons for the endoplasmic reticulum lumen.

PaperPlayer biorxiv cell biology

Play Episode Listen Later Jun 22, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.21.546000v1?rss=1 Authors: Sharninghausen, R., Hwang, J., Dennison, D., Baldridge, R. Abstract: Degrons are the minimal features that target proteins for degradation. In most cases, degrons allow recognition by components of the cytosolic ubiquitin proteasome system. Currently, every degron that has been identified only functions within the cytosol. Using Saccharomyces cerevisiae, we identified the first short linear sequences that function as degrons from the endoplasmic reticulum (ER) lumen. We show that when these degrons are transferred to proteins, they facilitate degradation through the ERAD system at the cytosolic proteasome. These degrons enable degradation of both luminal and integral membrane ER proteins, expanding the types of proteins that can be targeted for degradation both in budding yeast and in mammalian tissue culture. This discovery provides a framework to target proteins for degradation from the previously unreachable ER lumen and enables novel therapeutic approaches that exploit the highly-conserved ERAD system. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
The endoplasmic reticulum stress sensor IRE1 regulates collagen secretion through the enforcement of the proteostasis factor P4HB/PDIA1 contributing to liver damage and fibrosis

PaperPlayer biorxiv cell biology

Play Episode Listen Later May 2, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.02.538835v1?rss=1 Authors: Hazari, Y., Urra, H., Lopez, V. A. G., Diaz, J., Tamburini, G., Milani, M., Pihan, P., Durand, S., Aprahamia, F., Baxter, R., Huang, M., Dong, X. C., Vihinen, H., Gonzalez, A. B., Godoy, P., Criollo, A., Ratziu, V., Foufelle, F., Hengstler, J. G., Jokitalo, E., Maitre, B. B., Maiers, J. L., Plate, L., Kroemer, G., Hetz, C. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Simultaneous photoactivation and high-speed structural tracking reveal diffusion-dominated motion in the endoplasmic reticulum

PaperPlayer biorxiv cell biology

Play Episode Listen Later Apr 25, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.23.537908v1?rss=1 Authors: Dora, M., Obara, C. J., Abel, T., Lippincott-Schwartz, J., Holcman, D. Abstract: The endoplasmic reticulum (ER) is a structurally complex, membrane-enclosed compartment that stretches from the nuclear envelope to the extreme periphery of eukaryotic cells. The organelle is crucial for numerous distinct cellular processes, but how these processes are spatially regulated within the structure is unclear. Traditional imaging-based approaches to understanding protein dynamics within the organelle are limited by the convoluted structure and rapid movement of molecular components. Here, we introduce a combinatorial imaging and machine learning-assisted image analysis approach to track the motion of photoactivated proteins within the ER of live cells. We find that simultaneous knowledge of the underlying ER structure is required to accurately analyze fluorescently-tagged protein redistribution, and after appropriate structural calibration we see all proteins assayed show signatures of Brownian diffusion-dominated motion over micron spatial scales. Remarkably, we find that in some cells the ER structure can be explored in a highly asymmetric manner, likely as a result of uneven connectivity within the organelle. This remains true independently of the size, topology, or folding state of the fluorescently-tagged molecules, suggesting a potential role for ER connectivity in driving spatially regulated biology in eukaryotes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Dextromethorphan inhibits collagen transport in the endoplasmic reticulum eliciting an anti-fibrotic response in ex-vivo and in vitro models of pulmonary fibrosis

PaperPlayer biorxiv cell biology

Play Episode Listen Later Apr 19, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.19.537530v1?rss=1 Authors: Khan, M. M., Zukowska, J., Jung, J., Galea, G., Tuechler, N., Halavatyi, A., Tischer, C., Haberkant, P., Stein, F., Jung, F., Landry, J., Khan, A. M., Oorschot, V., Becher, I., Neumann, B., Muley, T., Winter, H., Duerr, J., Mall, M., Savitski, M., Pepperkok, R. Abstract: Excessive deposition of fibrillar collagen in the interstitial extracellular matrix (ECM) of human lung tissue causes fibrosis, which can ultimately lead to organ failure. Despite our understanding of the molecular mechanisms underlying the disease, a cure for pulmonary fibrosis has not yet been found. In this study, we screened an FDA-approved drug library containing 712 drugs and found that Dextromethorphan (DXM), a cough expectorant, significantly reduces the amount of excess fibrillar collagen deposited in the ECM in in-vitro cultured primary human lung fibroblasts (NHLF) and ex-vivo cultured human precision-cut lung slice (hPCLS) models of lung fibrosis. Reduced extracellular fibrillar collagen levels in the ECM upon DXM treatment are due to a reversible trafficking inhibition of collagen type I (COL1) in the endoplasmic reticulum (ER) in TANGO1 and HSP47 positive structures. Mass spectrometric analysis shows that DXM causes hyper-hydroxylation of proline and lysine residues on Collagen (COL1, COL3, COL4, COL5, COL7, COL12) and Latent-transforming growth factor beta-binding protein (LTBP1 and LTBP2) peptides coinciding with their secretion block. In addition, thermal proteome profiling of cells treated with DXM shows increased thermal stability of prolyl- hydroxylases such as P3H2, P3H3, P3H4, P4HA1 and P4HA2, suggesting a change in activity. Transcriptome analysis of pro-fibrotic stimulated NHLFs and hPCLS upon DXM treatment showed activation of an anti-fibrotic program via regulation of pathways such as those involved in the MMP-ADAMTS axis, WNT, and fibroblast-to-myofibroblast differentiation. Taken together, the data obtained from both in-vitro and ex-vivo models of fibrogenesis show that Dextromethorphan has potent anti-fibrotic activity by efficient inhibition of COL1 membrane trafficking in the ER. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Adapting the endoplasmic reticulum proteostasis rescues epilepsy-associated NMDA receptor variants

PaperPlayer biorxiv cell biology

Play Episode Listen Later Apr 2, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.01.535233v1?rss=1 Authors: Zhang, P.-P., Benske, T. M., Paton, J. C., Paton, A. W., Mu, T., Wang, Y.-J. Abstract: The GRIN genes encoding N-methyl-D-aspartate receptor (NMDAR) subunits are remarkably intolerant to variation. Many pathogenic NMDAR variants result in their protein misfolding, inefficient assembly, reduced surface expression, and impaired functionality at the plasma membrane, causing neurological disorders including epilepsy and intellectual disability. Here, we concentrate on the proteostasis maintenance of NMDARs containing epilepsy-associated variations in the GluN2A (or NR2A) subunit, including M705V and A727T. We showed that these two variants are targeted to the proteasome for degradation and have reduced functional surface expression. We demonstrated that the application of BIX, a known small molecule activator of an HSP70 family chaperone BiP (Binding immunoglobulin Protein) in the endoplasmic reticulum (ER), significantly increases total and surface protein levels, and thus the function of the M705V and A727T variants in HEK293T cells. Mechanistic studies revealed that BIX promotes folding, inhibits degradation, and enhances anterograde trafficking of the M705V variant by modest activation of the IRE1 pathway of the unfolded protein response. Our results showed that adapting the ER proteostasis network restores the folding, trafficking, and function of pathogenic NMDAR variants, representing a potential treatment for neurological disorders resulting from NMDAR dysfunction. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
OSBP-mediated PI(4)P-cholesterol exchange at endoplasmic reticulum-secretory granule contact sites controls insulin secretion

PaperPlayer biorxiv cell biology

Play Episode Listen Later Feb 22, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.22.529485v1?rss=1 Authors: Panagiotou, S., Nguyen, P. M., Tan, K.-W., Mueller, A., Wendt, A., Eliasson, L., Tengholm, A., Solimena, M., Idevall-Hagren, O. Abstract: Insulin secretion is the process whereby insulin-containing granules fuse with the plasma membrane of {beta}-cells. Exocytosis is preceded by cargo loading, maturation and transport of the secretory granules; processes that require modification of both the protein and lipid composition of the granules. We recently identified phosphatidylinositol-4 phosphate (PI[4]P) dephosphorylation by INPP5F/Sac2 on the surface of insulin granules as a key step that precedes stable granule docking at the plasma membrane and that is required for normal insulin secretion. Here, we show that PI(4)P is used to target the lipid exchange protein oxysterol-binding protein (OSBP) to the granule surface where it is involved in PI(4)P/cholesterol exchange. Loss of Sac2 resulted in excess accumulation of cholesterol on insulin granules that was normalized when OSBP expression was reduced. Acute inhibition of OSBP resulted in dramatic cellular redistribution of OSBP to insulin granules where it colocalized with the ER-resident protein VAP-A at ER-granule contact sites. Stimulation of insulin secretion also resulted in translocation of OSBP to the insulin granule surface in a process that depended on Ca2+-induced acidification of the cytosol. Similar to Sac2 knockdown, inhibition of OSBP suppressed insulin secretion without affecting insulin production. In conclusion, we show that lipid exchange at ER-granule contacts sites is involved in the exocytic process, and propose that these contacts act as reaction centers with multimodal functions during insulin granule maturation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
The junctions connecting the endoplasmic reticulum to the nuclear envelope are constricted and remodelled during the cell cycle

PaperPlayer biorxiv cell biology

Play Episode Listen Later Feb 1, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.31.526419v1?rss=1 Authors: Bragulat-Teixidor, H., Ishihara, K., Szucs, G. M., Otsuka, S. Abstract: The endoplasmic reticulum (ER) is physically connected to the cell nucleus via junctions with the nuclear envelope (NE). These ER-NE junctions are essential for supplying the NE with lipids and transmembrane proteins that are synthesized in the ER. Despite the important role of ER-NE junctions, their biogenesis, architecture and maintenance across the cell cycle has remained elusive. In this study, by combining live cell imaging with quantitative three-dimensional electron microscopy, we systematically elucidated the ultrastructure of ER-NE junctions in mammalian cells. We discovered that ER-NE junctions exhibit a constricted hourglass shape that is different from the junctions within the ER. When ER-NE junctions are newly built during NE assembly at mitotic exit, their morphology resembles ER-ER junctions, but they become constricted starting in telophase. Altogether, our findings imply novel mechanisms that remodel ER-NE junctions and have functional implications for the lipid and protein traffic that are crucial for nuclear function. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
The nanoscale organization of reticulon 4 shapes local endoplasmic reticulum structure in situ

PaperPlayer biorxiv cell biology

Play Episode Listen Later Jan 27, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.26.525608v1?rss=1 Authors: Fuentes, L. A., Marin, Z., Tyson, J., Baddeley, D., Bewersdorf, J. Abstract: The endoplasmic reticulums (ER) structure is directly linked to the many functions of the ER but its formation is not fully understood. We investigate how the ER-membrane curving protein reticulon 4 (Rtn4) localizes to and organizes in the membrane and how that affects local ER structure. We show a strong correlation between the local Rtn4 density and the local ER membrane curvature. Our data further reveal that the typical ER tubule possesses an elliptical cross-section with Rtn4 enriched at either end of the major axis. Rtn4 oligomers are linear-shaped, contain about five copies of the protein, and preferentially orient parallel to the tubule axis. Our observations support a mechanism in which oligomerization leads to an increase of the local Rtn4 concentration with each molecule increasing membrane curvature through a hairpin wedging mechanism. This quantitative analysis of Rtn4 and its effects on the ER membrane result in a new model of tubule shape as it relates to Rtn4. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
The YAP-TEAD complex promotes senescent cell survival by lowering endoplasmic reticulum stress

PaperPlayer biorxiv cell biology

Play Episode Listen Later Dec 19, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.18.520921v1?rss=1 Authors: Anerillas, C., Mazan-Mamczarz, K., Herman, A. B., Munk, R., Lam, G. K., Calvo-Rubio, M., Garrido, A., Tsitsipatis, D., Martindale, J. L., Altes, G., Rossi, M., Piao, Y., Fan, J., Cui, C.-Y., De, S., Abdelmohsen, K., de Cabo, R., Gorospe, M. Abstract: Sublethal cell damage can trigger a complex adaptive program known as senescence, characterized by growth arrest, resistance to apoptosis, and a senescence-associated secretory phenotype (SASP). As senescent cells accumulating in aging organs are linked to many age-associated diseases, senotherapeutic strategies are actively sought to eliminate them. Here, a whole-genome CRISPR knockout screen revealed that proteins in the YAP-TEAD pathway influenced senescent cell viability. Accordingly, treating senescent cells with a drug that inhibited this pathway, Verteporfin (VPF), selectively triggered apoptotic cell death and derepressed DDIT4, in turn inhibiting mTOR. Reducing mTOR function in senescent cells diminished endoplasmic reticulum (ER) biogenesis, causing ER stress and apoptosis due to high demands on ER function by the SASP. Importantly, VPF treatment decreased senescent cell numbers in the organs of old mice and mice exhibiting doxorubicin-induced senescence. We present a novel senolytic strategy that eliminates senescent cells by hindering ER activity required for SASP production. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Lipid Biosynthesis Perturbation Impairs Endoplasmic Reticulum-Associated Degradation

PaperPlayer biorxiv cell biology

Play Episode Listen Later Dec 10, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.09.519544v1?rss=1 Authors: Turk, S. M., Indovina, C. J., Overton, D. L., Runnebohm, A. M., Orchard, C. J., Doss, E. M., Richards, K. A., Irelan, C. B., Daraghmi, M. M., Bailey, C. G., Miller, J. M., Niekamp, J. M., Gosser, S. K., Tragesser-Tina, M. E., Claypool, K. P., Engle, S. M., Buchanan, B. W., Woodruff, K. A., Olesen, J. B., Smaldino, P. J., Rubenstein, E. M. Abstract: The relationship between lipid homeostasis and protein homeostasis (proteostasis) is complex and remains incompletely understood. We conducted a screen for genes required for efficient degradation of Deg1-Sec62, a model aberrant translocon-associated substrate of the endoplasmic reticulum (ER) ubiquitin ligase Hrd1, in Saccharomyces cerevisiae. This screen revealed that INO4 is required for efficient Deg1-Sec62 degradation. INO4 encodes one subunit of the Ino2/Ino4 heterodimeric transcription factor, which regulates expression of genes required for lipid biosynthesis. Deg1-Sec62 degradation was also impaired by mutation of genes encoding several enzymes mediating phospholipid and sterol biosynthesis. The degradation defect in ino4{Delta} yeast was rescued by supplementation with metabolites whose synthesis and uptake are mediated by Ino2/Ino4 targets. Stabilization of a panel of substrates of the Hrd1 and Doa10 ER ubiquitin ligases by INO4 deletion indicates ER protein quality control is generally sensitive to perturbed lipid homeostasis. Further, loss of INO4 sensitized yeast to proteotoxic stress, suggesting a broad requirement for lipid homeostasis in maintaining proteostasis. Abundance of the ER ubiquitin-conjugating enzyme Ubc7 was reduced in the absence of INO4, consistent with a model whereby perturbed lipid biosynthesis alters the abundance of critical protein quality control mediators, with broad consequences for ER proteostasis. A better understanding of the dynamic relationship between lipid homeostasis and proteostasis may lead to improved understanding and treatment of several human diseases associated with altered lipid biosynthesis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
SAYSD1 senses UFMylated ribosome to safeguard co-translational protein translocation at the endoplasmic reticulum

PaperPlayer biorxiv cell biology

Play Episode Listen Later Dec 7, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.05.519155v1?rss=1 Authors: Wang, L., Xu, Y., Yun, S., Yuan, Q., Satpute-Krishnan, P., Ye, Y. Abstract: Translocon clogging at the endoplasmic reticulum (ER) as a result of translation stalling triggers ribosome UFMylation, activating a Translocation-Associated Quality Control (TAQC) mechanism that degrades clogged substrates. How cells sense ribosome UFMylation to initiate TAQC is unclear. Here we use a genome-wide CRISPR/Cas9 screen to identify an uncharacterized membrane protein named SAYSD1 that facilitates TAQC. SAYSD1 associates with the Sec61 translocon, and also recognizes both ribosome and UFM1 directly, engaging a stalled nascent chain to ensure its transport via the TRAPP complex to lysosomes for degradation. Like UFM1 deficiency, SAYSD1 depletion causes the accumulation of translocation-stalled proteins at the ER and triggers ER stress. Importantly, disrupting UFM1- and SAYSD1-dependent TAQC in Drosophila leads to intracellular accumulation of translocation-stalled collagens, defective collagen deposition, abnormal basement membranes, and reduced stress tolerance. Together, our data support a model that SAYSD1 acts as a UFM1 sensor that collaborates with ribosome UFMylation at the site of clogged translocon, safeguarding ER homeostasis during animal development. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
ESYT1 tethers the endoplasmic reticulum to mitochondria and is required for mitochondrial lipid and calcium homeostasis

PaperPlayer biorxiv cell biology

Play Episode Listen Later Nov 15, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.14.516495v1?rss=1 Authors: janer, a., Morris, J. l., krols, m., Antonicka, H., aaltonen, m. j., Lin, Z.-Y., Gingras, A.-C., Prudent, J., shoubridge, e. a. Abstract: Mitochondria interact with the endoplasmic reticulum (ER) at structurally and functionally specialized membrane contact sites known as mitochondria-ER contact sites (MERCs). MERCs are crucial for a myriad of physiological functions including lipid synthesis and transport, and calcium signaling. Alterations in the structure, composition or regulation of MERCs contribute to the aetiology of many pathologies including neurodegenerative and metabolic diseases. The proteins mediating the formation of MERCs have been extensively studied in yeast, where the ER-mitochondria encounter structure (ERMES) complex mediates the transport of lipids between the ER and mitochondria via three lipid binding SMP-domain proteins. However, none of the SMP proteins of the ERMES complex have orthologues in mammals suggesting that alternate pathways have evolved in metazoans. Combining proximity labelling (BioID), confocal microscopy and subcellular fractionation, we found that the ER resident SMP-domain containing protein ESYT1 was enriched at MERCs, where it forms a complex with the outer mitochondrial membrane protein SYNJ2BP. The deletion of ESYT1 or SYNJ2BP reduced the number and length of MERCs, indicating that the ESYT1-SYN2JBP complex plays a role in tethering ER and mitochondria. Loss of this complex impaired ER to mitochondria calcium flux and provoked a significant alteration of the mitochondrial lipidome, most prominently a reduction of cardiolipins and phosphatidylethanolamines. Both phenotypes were rescued by re-expression of wild-type ESYT1 as well as an artificial mitochondria-ER tether. Together, these results reveal a novel function of ESYT1 in mitochondrial and cellular homeostasis through its role in the regulation of MERCs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Neurons Alter Endoplasmic Reticulum Exit Sites to accommodate Dendritic Arbor Size

PaperPlayer biorxiv cell biology

Play Episode Listen Later Nov 4, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.03.515099v1?rss=1 Authors: Land, R. H., Fetter, R. D., Liang, X., Tzeng, C., Shen, K. Abstract: Nervous systems exhibit dramatic diversity in cell morphology and size. How neurons regulate their biosynthetic and secretory machinery to support different cell sizes is not well understood. Endoplasmic reticulum exit sites (ERESs) are essential for maintaining secretory flux, and are required for normal dendrite development.1 However, it is unknown how neurons of different size regulate the number of secretory structures to accommodate morphogenesis. In C. elegans, we find that ERES number is strongly correlated with the size of a neuron's dendritic arbor. The elaborately branched sensory neuron, PVD, has especially high ERES numbers in its soma. PVD establishes its high ERES number rapidly after birth, actively maintains ERES number as PVD grows and matures. The initial high number of ERES in PVD is driven by asymmetric cell division producing a large cell size at birth. Subsequent maintenance of ERES number requires the cell fate transcription factor MEC-3 and C. elegans TOR (ceTOR/let-363). This ceTOR/let-363 pathway integrates nutrient availability to coordinate ERES number with soma size and dendritic expansion. Our results are consistent with a model in which transcription factors, master metabolic regulators and nutrient availability coordinate to specify developmental parameters including soma size, ERES number and dendrite size, which together determine neuronal cell fate. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Hsp47 Promotes Biogenesis of Multi-subunit Neuroreceptors in the Endoplasmic Reticulum

PaperPlayer biorxiv cell biology

Play Episode Listen Later Oct 26, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.24.513629v1?rss=1 Authors: Wang, Y.-J., Di, X.-J., Han, D.-Y., Nashmi, R., Henderson, B. J., Moss, F. J., Mu, T.-W. Abstract: Protein homeostasis (proteostasis) deficiency is recognized as a contributing factor to many neurodegenerative, neurological, and metabolic diseases. However, how the proteostasis network orchestrates the folding and assembly of multi-subunit membrane proteins is not completely understood. In this investigation, we focus on characterizing the biogenesis pathway of a multi-subunit neuroreceptor, the gamma-aminobutyric acid type A (GABAA) receptor. Previous proteomics studies identified Hsp47 (Gene: SERPINH1), a heat shock protein in the endoplasmic reticulum lumen, as the most enriched GABAA receptor-interacting chaperone. Here, we show that Hsp47 enhances neuronal GABAA receptor functional surface expression, acting after Binding immunoglobulin Protein (BiP), to preferentially bind the folded conformation of GABAA receptors. Therefore, Hsp47 promotes the subunit-subunit interaction, the receptor assembly process, and the anterograde trafficking of GABAA receptors. These Hsp47 properties are also extended to other Cys-loop receptors, including nicotinic acetylcholine receptors. Therefore, in addition to its known function as a collagen chaperone, this work establishes that Hsp47 also plays a critical and general role in the maturation of multi-subunit neuroreceptors. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Arc ubiquitination regulates endoplasmic reticulum-mediated Ca2+ release and CaMKII signaling

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Sep 4, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.02.506383v1?rss=1 Authors: Ghane, M. A., Allen, Z. D., Miller, C. L., Dong, B., Fang, N., Yang, J. J., Mabb, A. M. Abstract: Synaptic plasticity relies on rapid, yet spatially precise signaling to alter synaptic strength. Arc is a brain enriched protein that is rapidly expressed during learning-related behaviors and is essential for regulating metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD). We previously showed that disrupting the ubiquitination capacity of Arc enhances mGluR-LTD; however, the mechanism by which this occurs and its consequences on other mGluR-mediated signaling events is unknown. Here we show that disrupting Arc ubiquitination on key amino acid residues leads to derangements in Ca2+ release from the endoplasmic reticulum (ER) during pharmacological activation of Group I mGluRs. These alterations were observed in all neuronal subregions except secondary branchpoints. Deficits in Arc ubiquitination increased Arc self-association and enhanced its interaction with calcium/calmodulin-dependent protein kinase IIb (CaMKIIb) and constitutively active forms of CaMKII. Notably, these interactions were also excluded at secondary branchpoints. Finally, disruptions in Arc ubiquitination were found to increase Arc interaction with the integral ER protein Calnexin. These results suggest a previously unknown role for Arc ubiquitination in the fine tuning of ER-mediated Ca2+ signaling that is needed for mGluR-LTD, which, in turn, regulates CaMKII-dependent regulation of Arc. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Dr. Eric's Relentless Vitality
Anabolic Resistance and Endoplasmic Reticular Stress

Dr. Eric's Relentless Vitality

Play Episode Listen Later Jul 25, 2022 5:24


Dr. Eric continues his series on Anabolic Resistance. This is an important section that explains how cellular stress in the Endoplasmic Reticulum leads to the final pathway of damage and why it is important to understand this!

The Medbullets Step 1 Podcast
Biochemistry | Endoplasmic Reticulum

The Medbullets Step 1 Podcast

Play Episode Listen Later Mar 25, 2022 10:22


In this episode, we review the high-yield topic of Endoplasmic Reticulum from the Biochemistry section. Follow Medbullets on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbulletsIn this episode --- Send in a voice message: https://anchor.fm/medbulletsstep1/message

Kidney360
Article Summary by Kensei Taguchi, Craig R Brooks, and Bertha C Elias

Kidney360

Play Episode Listen Later Dec 30, 2021 9:20


This is an article summary of "Quantitative super-resolution microscopy reveals promoting mitochondrial interconnectivity protects against AKI" by Kensei Taguchi, Craig R Brooks, and Bertha C Elias on behalf of coauthors.

Aging-US
Suppressing Endoplasmic Reticulum Stress-related Autophagy

Aging-US

Play Episode Listen Later Nov 18, 2021 1:57


Aging-US published a Special Collection on Eye Disease which included "Suppressing endoplasmic reticulum stress-related autophagy attenuates retinal light injury" which reported that in this study, oxidative stress, endoplasmic reticulum stress and autophagy caused by light exposure were evaluated in vitro and in vivo. Additionally, inhibiting ER stress either by knocking down PERK signals or with GSK2606414 treatment remarkably suppressed prolonged autophagy and protected the cells against light injury. In vivo experiments verified neuroprotection via inhibiting ER stress-related autophagy in light-damaged retinas of mice. In conclusion, the above results suggest that light-induced photo-oxidative stress may trigger subsequent activation of ER stress and prolonged autophagy in photoreceptors and RPE cells. Suppressing ER stress may abrogate over-activated autophagy and protect the retina against light injury. Dr. Guang-Yu Li from The Second Hospital of Jilin University said, "Age-related macular degeneration (AMD) is a degenerative retinal disease, which often occurs in the elderly and causes irreversible loss of central vision." Indeed, excessive and prolonged light exposure may damage the retina and is an environmental factor that can accelerate AMD. With the rapid development of technology, many electronic devices with screens, and ophthalmic equipment with intensive illumination, have become widely used. Therefore, an increasing amount of attention has been focused on issues of light pollution and retinal light damage. Previous studies have shown that excessive intracellular ROS may lead to depletion of the GSH pool and compromise the function of PDI, which disrupts the folding process of proteins in the ER and produces a massive amount of misfolded proteins. However, the excessive accumulation of misfolded proteins in the ER may trigger an unfolded-protein response, which may enhance protein folding ability, as well as the homeostasis of protein translation and accelerate protein degradation to recover ER function. However, prolonged autophagy may lead to cell death and is specifically termed autophagy-dependent cell death. The role of autophagy in retinal light injury is controversial. Autophagy might be a double-edged sword among the molecular mechanisms that lead to retinal light damage. Midorikawa et al. reported that moderate autophagy combined with endosomal degradation pathway activity is neuroprotective and attenuates light-dependent retinal degeneration. The Li Research Team concluded in their Aging-US Research Output "the current study demonstrated that ER stress and autophagy are both involved in light-induced death of photoreceptors and RPE cells. As an upstream step, photo-oxidation may cause an imbalance in the cellular redox status and interrupt the folding process of proteins, further triggering ER stress in photoreceptors and RPEs. Suppressing ER stress via PERK signals may inhibit prolonged autophagy and protect photoreceptors/RPEs against light damage. Inhibiting ER stress-related autophagy is neuroprotective for retinal against light injury, which may be a potential treatment strategy for AMD." Full Text - https://www.aging-us.com/article/103846/text Correspondence to: Guang-Yu Li email: l_gy@jlu.edu.cn Keywords: oxidative stress, ER stress, autophagy, AMD, PERK

Assignment Help In Australia
Get The Best Biology Assignment Help In Australia

Assignment Help In Australia

Play Episode Listen Later Apr 19, 2021 1:24


Our experts providing you with the best Biology assignment help Australia are capable of assisting with the terms and terminologies such as Ribosomes, RNA, Lysosomes. Chloroplasts, Vacuoles, Endoplasmic Reticulum, and much more. We have more than 400 Biology assignment help experts who are there with us and have more than 12 experience in the corresponding discipline.

Assignment Help In Australia
Biology Assignment Help In Australia

Assignment Help In Australia

Play Episode Listen Later Feb 1, 2021 1:14


Give all your Biology assignment help online queries a strategic direction by diverting your problems to My Assignment Services. Our experts providing you with the best Biology assignment help Australia are capable of assisting with the terms and terminologies such as Ribosomes, RNA, Lysosomes. Chloroplasts, Vacuoles, Endoplasmic Reticulum, and much more. We have more than 400 Biology assignment help experts who are there with us and have more than 12 experience in the corresponding discipline. By choosing our assignment help experts, you get a chance to prepare a 100% original and plagiarism free assessment tasks at a minimal price.

australia biology assignment rna endoplasmic reticulum lysosomes chloroplasts my assignment services
MCAT Flash Go | Question Of The Day | MCAT Prep, Review, Strategy And Tips To Ace The MCAT!
#39: Endoplasmic Reticulum | Biological and Biochemical Foundations of Living Systems | MCAT Question Of The Day | Prep, Study Tips, And Strategies for Pre-Med Students

MCAT Flash Go | Question Of The Day | MCAT Prep, Review, Strategy And Tips To Ace The MCAT!

Play Episode Listen Later Dec 24, 2020 4:27


In this episode, Austin Santiago asks a question about the endoplasmic reticulum. This is a question you might see from the Biological and Biochemical Foundations of Living Systems section. This podcast is designed for Pre-medical students preparing to take their Medical College Admissions Test (MCAT). This episode is powered by Premed Consultants, an all-inclusive premed advising program. Whether you are starting out as a freshman or about to start prepping for the MCAT, the premed consultants will help you throughout your entire premed process until you get into medical school. Not only is there a full MCAT program utilizing the most effective study tactics, but they will also help you through the entire admissions process as well. If you're interested in one on one mentorship, go to thepremedconsultants.com and you can schedule a free 30 min strategy session to see if Premed Consultants is the right fit for you. If you have any suggestions, concerns, or question, feel free to e-mail us at mcatflashgo@gmail.com We wish you the best of luck on your educational journey!

Idea 2 Impact
From Robert Hook to Endoplasmic Reticulum: Science, Research, and Innovation

Idea 2 Impact

Play Episode Listen Later Dec 11, 2020 36:07


In this two-part episode, hosts Beth Deuermeyer and Jack Manhire sit down with Dr. Larry Griffing from the Department of Biology here at Texas A&M University. We discuss his research interests, Robert Hook, and his research with the endoplasmic reticulum. You may be asking yourself what these things have in common, but you will have to listen to find out. We also discuss his Innovation[X] project where he addresses the question, "How is a discovery in basic science translated into a product that can potentially be used for the general good, while also providing a large profit?". For more episodes, or information on how you can submit an Innovation[X] proposal, visit the Innovation Partners website.

BioTime
Endoplasmic Reticulum

BioTime

Play Episode Listen Later Nov 28, 2020 18:22


In this podcast, a major organelle of the Endomembrane system is discussed, the Endoplasmic Reticulum. The episode opens with a discussion on the ER as a whole and then goes into detail on the structure and function of the ER's two counterparts, the smooth and rough ER. If you have any questions, feel free to send them to https://anchor.fm/christopher-jang/message or https://2255christopher.wixsite.com/biotime/questions

PaperPlayer biorxiv biochemistry
Calcium depletion challenges endoplasmic reticulum proteostasis by destabilising BiP-substrate complexes

PaperPlayer biorxiv biochemistry

Play Episode Listen Later Nov 3, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.03.366484v1?rss=1 Authors: Preissler, S., Rato, C., Yan, Y., Perera, L. A., Czako, A., Ron, D. Abstract: The metazoan endoplasmic reticulum (ER) serves both as a hub for maturation of secreted proteins and as an intracellular calcium storage compartment, facilitating calcium release-dependent cellular processes. ER calcium depletion robustly activates the unfolded protein response (UPR). However, it is unclear how fluctuations in ER calcium impact organellar proteostasis. Here we report that calcium selectively affects the dynamics of the abundant metazoan ER Hsp70 chaperone BiP, by enhancing its affinity for ADP. In the calcium replete ER, ADP rebinding to post-ATP hydrolysis BiP-substrate complexes competes with ATP binding during both spontaneous and co-chaperone-assisted nucleotide exchange, favouring substrate retention. Conversely, in the calcium depleted ER, relative acceleration of ADP-to-ATP exchange favours substrate release. These findings explain the rapid dissociation of certain substrates from BiP observed in the calcium-depleted ER and suggest a mechanism for tuning ER quality control and coupling UPR activity to signals that mobilise ER calcium in secretory cells. Copy rights belong to original authors. Visit the link for more info

PaperPlayer biorxiv biochemistry
Activation of the membrane-bound Nrf1 transcription factor by USP19, a tail-anchored ubiquitin-specific protease in the endoplasmic reticulum

PaperPlayer biorxiv biochemistry

Play Episode Listen Later Oct 6, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.05.326363v1?rss=1 Authors: Shaofan, H., Yuancai, X., Lu, Q., Meng, W., Zhang, Y. Abstract: The membrane-bound transcription factor Nrf1 (i.e., encoded by Nfe2l1) is activated by sensing glucose deprivation, cholesterol excess, proteasomal inhibition and oxidative stress, and then mediates distinct signaling responses in order to maintain cellular homeostasis. Here, we found that Nrf1 stability and transactivity are enhanced by USP19, a tail-anchored ubiquitin-specific protease in the endoplasmic reticulum (ER). Further experiments revealed that USP19 directly interacts with Nrf1 in proximity to the ER and acts as a deubiquitinating enzyme to remove ubiquitin moieties from this protein and hence circumvent potential proteasomal degradation. Such USP19-mediated effect takes place only after Nrf1 is retrotranslocated by p97 out of ER membranes. Conversely, knockout of USP19 causes significant decreases in Nrf1 abundance and its active isoform entering the nucleus, resulting in down-regulation of its target proteasomal subunits. This led to a modest reduction of USP19-/-derived tumor growth in xenograft mice, when compared with wild-type controls. Altogether, these demonstrate that USP19 serves as a novel mechanistic modulator of Nrf1, but not Nrf2. In turn, our additional evidence has also unraveled that transcriptional expression of endogenous USP19 and its promoter-driven reporter genes is regulated by Nrf2, as well by Nrf1, at distinct layers within a complex hierarchical regulatory network. Copy rights belong to original authors. Visit the link for more info

PaperPlayer biorxiv neuroscience
Synaptic anchoring of the endoplasmic reticulum depends on myosin V and caldendrin activity

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Aug 15, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.14.250746v1?rss=1 Authors: Konietzny, A., Grendel, J., Hertrich, N., Dekkers, D. H. W., Demmers, J. A., Mikhaylova, M. Abstract: Excitatory synapses of principal hippocampal neurons are frequently located on dendritic spines. The dynamic strengthening or weakening of individual inputs results in a great structural and molecular diversity of dendritic spines. Active spines with large Ca2+ transients are frequently invaded by a single protrusion from the endoplasmic reticulum (ER), which is dynamically transported into and out of spines by the actin-based motor myosin V. An increase in synaptic strength often correlates with stable anchoring of the ER, followed by the formation of the spine apparatus organelle. Here we show that synaptic ER stabilization depends on the interplay of two Ca2+-binding proteins: calmodulin serves as a light chain of myosin V and activates the motor function, whereas caldendrin acts as an inhibitor which transforms myosin into a stationary F-actin tether. Together, they provide a Ca2+-sensing module for fine-tuning myosin V activity and thereby regulate the formation of the spine apparatus in a subset of active dendritic spines. Copy rights belong to original authors. Visit the link for more info

PaperPlayer biorxiv neuroscience
Age and dose-dependent effects of alpha-lipoic acid on human microtubule-associated protein tau-induced endoplasmic reticulum unfolded protein response: implications for Alzheimers disease

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Aug 3, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.31.230847v1?rss=1 Authors: Zarini-Gakiye, E., Sanadgol, N., Parivar, K., Vaezi, G. Abstract: Background: In human tauopathies, pathological aggregation of misfolded/unfolded proteins particularly microtubule-associated protein tau (MAPT, tau) is considered to be essential mechanisms that trigger the induction of endoplasmic reticulum (ER) stress. Here we assessed the molecular effects of natural antioxidant alpha-lipoic acid (ALA) in human tauR406W (htau)-induced ER unfolded protein response (ERUPR) in the young and older flies. Methods: In order to reduce htau neurotoxicity during brain development, we used a transgenic model of tauopathy where the maximum toxicity was observed in adult flies. Then, the effects of ALA (0.001, 0.005, and 0.025% w/w of diet) in htau-induced ERUPR in the ages 20 and 30 days were evaluated. Results: Data from expression (mRNA and protein) patterns of htau, analysis of eyes external morphology as well as larvae olfactory memory were confirmed our tauopathy model. Moreover, expression of ERUPR-related proteins involving activating transcription factor 6 (ATF6), inositol regulating enzyme 1 (IRE1), and protein kinase RNA-like ER kinase (PERK) were upregulated and locomotor function decreased in both ages of the model flies. Remarkably, the lower dose of ALA modified ERUPR and supported the reduction of behavioral deficits in youngest adults through enhancement of GRP87/Bip, reduction of ATF6, downregulation of PERK-ATF4 pathway, and activation of the IRE1-XBP1 pathway. On the other hand, only a higher dose of ALA was able to affect the ERUPR via moderation of PERK-ATF4 signaling in the oldest adults. As ALA exerts their higher protective effects on the locomotor function of younger adults when htauR406W expressed in all neurons (htau-elav) and mushroom body neurons (htau-ok), we proposed that ALA has age-dependent effects in this model. Conclusion: Taken together, based on our results we conclude that aging potentially influences the ALA effective dose and mechanism of action on tau-induced ERUPR. Further molecular studies will warrant possible therapeutic applications of ALA in age-related tauopathies. Copy rights belong to original authors. Visit the link for more info

PaperPlayer biorxiv neuroscience
Endoplasmic reticulum visits highly active spines and prevents runaway potentiation of synapses

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Jul 30, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.30.228155v1?rss=1 Authors: Perez-Alvarez, A., Yin, S., Schulze, C., Hammer, J. A., Wagner, W., Oertner, T. G. Abstract: In hippocampal pyramidal cells, a small subset of dendritic spines contain endoplasmic reticulum (ER). In large spines, ER frequently forms a spine apparatus, while smaller spines contain just a single tubule of smooth ER. Here we show that the ER visits dendritic spines in a non-random manner, targeting spines during periods of high synaptic activity. When we blocked ER motility using a dominant negative approach against myosin V, spine synapses became stronger compared to controls. We were not able to further potentiate these maxed-out synapses, but LTD was readily induced by low-frequency stimulation. We conclude that the brief ER visits to active spines have the important function of preventing runaway potentiation of individual spine synapses, keeping most of them at an intermediate strength level from which both LTP and LTD are possible. Copy rights belong to original authors. Visit the link for more info

PaperPlayer biorxiv neuroscience
Neuronal autophagy regulates presynaptic neurotransmission by controlling the axonal endoplasmic reticulum

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Jul 6, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.06.189522v1?rss=1 Authors: Kuijpers, M., Kochlamazashvili, G., Stumpf, A., Puchkov, D., Lucht, M. T., Krause, E., Schmitz, D., Haucke, V. Abstract: Information processing in the brain is encoded as electrical impulses in neurons that are relayed from the presynaptic compartment to postsynaptic neurons by regulated neurotransmitter release. Neurons are known to rely on autophagy for the removal of defective proteins or organelles to maintain synaptic neurotransmission and to counteract neurodegeneration. In spite of its importance for neuronal health, the physiological substrates of neuronal autophagy in the absence of proteotoxic challenge have remained largely elusive. We use knockout mice conditionally lacking the essential autophagy protein ATG5 and quantitative proteomics to demonstrate that loss of neuronal autophagy causes the selective accumulation of tubular endoplasmic reticulum (ER) in axons, resulting in increased excitatory neurotransmission and compromised postnatal viability in vivo. The gain in excitatory neurotransmission is shown to be a consequence of elevated calcium release from ER stores via ryanodine receptors accumulated in axons and at presynaptic sites. We propose a model in which neuronal autophagy controls axonal ER calcium stores to regulate neurotransmission in healthy neurons and in the brain. Copy rights belong to original authors. Visit the link for more info

PaperPlayer biorxiv neuroscience
Indirect traumatic optic neuropathy after head trauma in adolescent male mice is associated with behavioral visual impairment, neurodegeneration, and elevated endoplasmic reticulum stress markers at acute and subacute times.

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Jun 12, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.11.144766v1?rss=1 Authors: Cansler, S. M., Guilhaume-Correa, F., Day, D., Bedolla, A., Evanson, N. K. Abstract: Traumatic brain injury (TBI) results in a number of impairments, often including visual symptoms. In some cases, visual symptoms after head trauma are mediated by traumatic injury to the optic nerve, termed traumatic optic neuropathy (TON), which has few options for treatment. Using a murine closed head model of head trauma, we have previously reported in adult mice that there is relatively selective injury to the optic system of the brain. In the current study, we performed blunt head trauma on adolescent C57BL/6 mice, and investigated visual impairment and retinal and optic system injury, using behavioral and histologic methods. After injury, mice display evidence of decreased optomotor responses, as evidence by decreased optokinetic nystagmus responses. There does not appear to be a significant change in circadian locomotor behavior patterns, although there is an overall decrease in locomotor behavior in mice with head injury. There is evidence of axonal degeneration of optic nerve fibers, with associated retinal ganglion cell death. There is also evidence of astrogliosis and microgliosis in major central targets of optic nerve projections. Further, there is elevated expression of markers of endoplasmic reticulum (ER) stress in retinas of injured mice. The current results extend our previous findings in adult mice into adolescent mice, provide direct evidence of retinal ganglion cell injury after head trauma, and suggest that axonal degeneration is associated with elevated ER stress in this model of TON. Visual impairment, histologic markers of gliosis and neurodegeneration, and elevated ER stress marker expression persist for at least 30 days after injury. Copy rights belong to original authors. Visit the link for more info

PaperPlayer biorxiv neuroscience
Precision genetic cellular models identify therapies protective against endoplasmic reticulum stress

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Jun 4, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.03.132886v1?rss=1 Authors: Lebedeva, I. V., Wagner, M. V., Sahdeo, S., Lu, Y.-F., Anyanwu-Ofili, A., Harms, M. B., Wadia, J. S., Rajagopal, G., Boland, M. J., Goldstein, D. B. Abstract: Congenital disorders of glycosylation (CDG) and deglycosylation (CDDG) are a collection of rare pediatric disorders with symptoms that range from mild to life threatening. They typically affect multiple organ systems and usually present with neurological abnormalities including hypotonia, cognitive impairment, and intractable seizures. Several genes have been implicated in the thirty-six types of CDG, but currently NGLY1 is the only known CDDG gene. A common biological mechanism among CDG types and in CDDG is endoplasmic reticulum (ER) stress. Here, we develop two isogenic human cellular models of CDG (PMM2, the most prevalent type of CDG, and DPAGT1) and of the only CDDG (NGYL1) in an effort to identify drugs that can alleviate ER stress. Systematic phenotyping identified elevated ER stress and autophagy levels among other cellular and morphological phenotypes in each of the cellular models. We screened a complex drug library for compounds able to correct aberrant morphological phenotypes in each of the models using an agnostic phenotypic cell painting assay based on >300 cellular features. The image-based screen identified multiple candidate compounds able to correct aberrant morphology, and we show a subset of these are able to correct cellular and molecular defects in each of the models. These results provide new directions for the treatment of rare diseases of glycosylation and deglycosylation and a framework for new drug screening paradigms for more common neurodegenerative diseases characterized by ER stress. Copy rights belong to original authors. Visit the link for more info

Out of the Blue: An AJRCCM Podcast
An Age-linked Role for Endoplasmic Reticulum Stress in Pulmonary Fibrosis

Out of the Blue: An AJRCCM Podcast

Play Episode Listen Later Mar 26, 2020 30:41


Dr. Maor Sauler sits down with Drs. Zea Borok, Michael Beers, Beiyun Zhou, and Jonathan Kropski to discuss the article "Grp78 Loss in Epithelial Progenitors Reveals an Age-linked Role for Endoplasmic Reticulum Stress in Pulmonary Fibrosis".

Dr. Berg’s Healthy Keto and Intermittent Fasting Podcast

Talk to a Dr. Berg Keto Consultant today and get the help you need on your journey (free consultation). Call 1-540-299-1557 with your questions about Keto, Intermittent Fasting, or the use of Dr. Berg products. Consultants are available Monday through Friday from 8:30 am to 9 pm EST. Saturday & Sunday 9 am to 5 pm EST. USA Only. Take Dr. Berg's Free Keto Mini-Course! Dr. Berg talks about what's inside your cells. There are many structures with specific functions. Dr. Berg explains these structures and breaks down the complexities. 1. Nucleus: DNA 2. RNA 3. Mitochondria 4. Endoplasmic Reticulum 5. Ribosomes 6. Glogi Apparatus 7. Lysosome 8. Peroxisome 9. Membranes Dr. Eric Berg DC Bio: Dr. Berg, 51 years of age is a chiropractor who specializes in weight loss through nutritional & natural methods. His private practice is located in Alexandria, Virginia. His clients include senior officials in the U.S. government & the Justice Department, ambassadors, medical doctors, high-level executives of prominent corporations, scientists, engineers, professors, and other clients from all walks of life. He is the author of The 7 Principles of Fat Burning. ABOUT DR. BERG: https://bit.ly/2FwSQQT DR. BERG'S STORY: https://bit.ly/2RwY5GP DR. BERG'S SHOP: https://bit.ly/2RN11yv DR. BERG'S VIDEO BLOG: https://bit.ly/2AZYyHt DR. BERG'S HEALTH COACHING TRAINING: https://bit.ly/2SZlH3o Follow us on FACEBOOK: https://www.messenger.com/t/drericberg TWITTER: https://twitter.com/DrBergDC YOUTUBE: https://www.youtube.com/user/drericberg123 Send a Message to Dr. Berg and his team: https://www.messenger.com/t/drericberg

Science Signaling Podcast
Science Signaling Podcast for 6 June 2017: Calcium signaling and dry mouth

Science Signaling Podcast

Play Episode Listen Later Jun 5, 2017 11:51


Indu Ambudkar explains why radiation therapy for head and neck cancers causes dry mouth.

Science Signaling Podcast
Science Signaling Podcast, 30 September 2014

Science Signaling Podcast

Play Episode Listen Later Sep 29, 2014 12:09


Amnon Altman describes how the guanine nucleotide exchange factor SLAT binds to IP3 receptor 1 at the endoplasmic reticulum to promote calcium release and T cell activation.

Science Signaling Podcast
Science Signaling Podcast, 2 September 2014

Science Signaling Podcast

Play Episode Listen Later Sep 1, 2014 14:33


Shulamit Michaeli talks about how the Trypanosoma brucei kinase PK3 inhibits new protein production in response to endoplasmic reticulum stress.

Molecular and Cellular Biology
G. Lederkremer - Endoplasmic reticulum stress in the pathogenesis of Huntington’s disease

Molecular and Cellular Biology

Play Episode Listen Later Nov 14, 2013 53:10


Gerardo Lederkremer Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, ISRAEL speaks on "Endoplasmic reticulum stress in the pathogenesis of Huntington’s disease". This seminar has been recorded by ICGEB Trieste

AGA Journals Video Podcast
IL-10 Promotes Production of Intestinal Mucus by Suppressing Protein Misfolding and Endoplasmic Reticulum Stress in Goblet Cells

AGA Journals Video Podcast

Play Episode Listen Later Apr 25, 2013 5:52


Drs. Michael McGuckin and Sumaira Z. Hasnain discuss their manuscript "IL-10 Promotes Production of Intestinal Mucus by Suppressing Protein Misfolding and Endoplasmic Reticulum Stress in Goblet Cells." Go to http://bit.ly/Y6pUiX.

Science Signaling Podcast
Science Signaling Podcast, 29 January 2013

Science Signaling Podcast

Play Episode Listen Later Jan 28, 2013 14:49


Vemurafenib induces endoplasmic reticulum stress in melanoma cells.

Medizin - Open Access LMU - Teil 21/22
4-Phenylbutyric Acid Reduces Endoplasmic Reticulum Stress, Trypsin Activation, and Acinar Cell Apoptosis While Increasing Secretion in Rat Pancreatic Acini

Medizin - Open Access LMU - Teil 21/22

Play Episode Listen Later Jan 1, 2013


Objectives: Endoplasmic reticulum (ER) stress leads to misfolded proteins inside the ER and initiates unfolded protein response (UPR). Unfolded protein response components are involved in pancreatic function and activated during pancreatitis. However, the exact role of ER stress in the exocrine pancreas is unclear. The present study examined the effects of 4-phenylbutyric acid (4-PBA), an ER chaperone, on acini and UPR components. Methods: Rat acini were stimulated with cholecystokinin (10 pmol/L to 10 nmol/L) with or without preincubation of 4-PBA. The UPR components were analyzed, including chaperone-binding protein, protein kinaselike ER kinase, X-box-binding protein 1, c-Jun NH2-terminal kinase, CCAAT/enhancer-binding protein homologous protein, caspase 3, and apoptosis. Effects of 4-PBA were measured on secretion, calcium, and trypsin activation. Results: 4-Phenylbutyric acid led to an increase of secretion, whereas trypsin activation with supraphysiological cholecystokinin was significantly reduced. 4-Phenylbutyric acid prevented chaperone-binding protein up-regulation, diminished protein kinaselike ER kinase, and c-Jun NH2-terminal kinase phosphorylation, prohibited X-box-binding protein 1 splicing and CCAAT/enhancer-binding protein homologous protein expression, caspase 3 activation, and apoptosis caused by supraphysiological cholecystokinin. Conclusion: By incubation with 4-PBA, beneficial in urea cycle deficiency, it was possible to enhance enzyme secretion to suppress trypsin activation, UPR activation, and proapoptotic pathways. The data hint new perspectives for the use of chemical chaperones in pancreatic diseases.

Intracellular transport - for iBooks

This unit explains the function of the cytoskeleton and its role in controlling transport of vesicles between different subcellular compartments. This study unit is just one of many that can be found on LearningSpace, part of OpenLearn, a collection of open educational resources from The Open University. Published in ePub 2.0.1 format, some feature such as audio, video and linked PDF are not supported by all ePub readers.

Medizin - Open Access LMU - Teil 16/22
Endoplasmic reticulum Ca2+-homeostasis is altered in small and non-small cell lung cancer cell lines

Medizin - Open Access LMU - Teil 16/22

Play Episode Listen Later Jan 1, 2009


Background: Knowledge of differences in the cellular physiology of malignant and non-malignant cells is a prerequisite for the development of cancer treatments that effectively kill cancer without damaging normal cells. Calcium is a ubiquitous signal molecule that is involved in the control of proliferation and apoptosis. We aimed to investigate if the endoplasmic reticulum (ER) Ca2+-homeostasis is different in lung cancer and normal human bronchial epithelial (NHBE) cells. Methods: The intracellular Ca2+-signaling was investigated using fluorescence microscopy and the expression of Ca2+-regulating proteins was assessed using Western Blot analysis. Results: In a Small Cell Lung Cancer (H1339) and an Adeno Carcinoma Lung Cancer (HCC) cell line but not in a Squamous Cell Lung Cancer (EPLC) and a Large Cell Lung Cancer (LCLC) cell line the ER Ca2+-content was reduced compared to NHBE. The reduced Ca2+-content correlated with a reduced expression of SERCA 2 pumping calcium into the ER, an increased expression of IP3R releasing calcium from the ER, and a reduced expression of calreticulin buffering calcium within the ER. Lowering the ER Ca2+-content with CPA led to increased proliferation NHBE and lung cancer cells. Conclusion: The significant differences in Ca2+-homeostasis between lung cancer and NHBE cells could represent a new target for cancer treatments.

Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 03/06
Coordination of endoplasmic reticulum and mRNA localization in Saccharomyces cerevisiae

Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 03/06

Play Episode Listen Later Jul 28, 2008


mRNA localization is a widespread mechanism in most eukaryotic cells to spatially restrict protein synthesis. During cell propagation of the budding yeast S. cerevisiae, mRNA localization is the basis for an asymmetric, stem-cell like division process. At least 24 transcripts are known to be localized to the yeast bud tip and the common core machinery mediating this mRNA translocation pathway consists of three components: the type V motor protein Myo4p, its adaptor She3p and the mRNA binding protein She2p. Recently, Myo4p and She3p were identified as essential factors of another bud-directed transport process, the inheritance of cortical endoplasmic reticulum (ER). In addition, live cell imaging revealed a co-localization and co-migration of localizing mRNPs with ER tubules that move to the yeast bud, implying for the first time that there might be a common transport of mRNAs and ER membranes. Within the scope of this study it was demonstrated that mutants defective in ER segregation are simultaneously impaired in mRNA localization indicating that there is indeed a connection between the two processes. Additionally, the RNA binding protein She2p associates with ER membranes in different sucellular fractionation assays and it does so independently of polysomes (thus, ongoing translation), mRNA and the Myo4p/She3p complex. During in vitro binding assays, recombinant She2p binds to flotation purified ER microsomes and protease treated membranes suggesting that She2p is not tethered to ER via a protein factor. Finally, She2p was found to have an inherent membrane binding activity since it directly associated with synthetic lipid vesicles in flotation assays. She2p attaches to liposomes also in presence of its RNA ligand excluding the possibility of an unspecific binding via its basic mRNA binding moiety. In summary, these data indicate that mRNA trafficking and ER inheritance are coordinated processes in S. cerevisiae and that She2p is the factor that tethers localizing mRNPs to the ER membranes. Consistent with this observation there is a growing number of examples from higher eukaryotes for a connection between membrane and mRNA transport. This in turn suggests that it is not a yeast specific phenomenon but rather might be a common theme throughout all kinds of eukaryotic species.

Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 02/06
Dynamics of Ribosome Association with the Endoplasmic Reticulum Membrane

Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 02/06

Play Episode Listen Later Sep 20, 2006


Protein translocation across the endoplasmic reticulum (ER) membrane is fundamental for protein sorting and secretion in all kingdoms. Translocation occurs through a protein-conducting channel in the ER membrane, which is formed by Sec61. Targeting of ribosome-nascent chain complexes (RNCs) to Sec61 is mediated by the signal recognition particle (SRP) and its cognate receptor (SR). However, Sec61 has a high affinity for nontranslating ribosomes and it is largely occupied in vivo. We addressed how RNC-SRP complexes can efficiently associate with the rER membrane, although most Sec61 seems to be occupied. We found that the spontaneous dissociation of ribosomes from the ER membrane is extremely slow. Surprisingly, membrane binding of RNC-SRP complexes does not require or cause the dissociation of prebound ribosomes. Instead, RNC-SRP complexes use a Sec61 population for translocation that cannot be bound by nontranslating ribosomes or RNCs alone. Complex formation between RNC-SRP and SR at the ER membrane facilitates the interaction between the RNC and the free Sec61. We have used biochemical and structural approaches to investigate why the free Sec61 fails to be bound by nontranslating ribosomes. Our data suggests that Sec61 is present in two interconvertible forms in the membrane, that are in an equilibrium with each other and provide high-affinity and low-affinity binding sites for ribosomes. The former are quickly occupied, while the latter remain free. The high-affinity binding sites are formed by tetrameric rings of Sec61, which provide several connections that each can break and reform, but together prevent the ribosome from detachment. In contrast, the low-affinity binding sites may correspond to lower oligomeric states of Sec61. Consistent with that, we could capture monomers or dimers of Sec61 bound to eukaryotic ribosomes by electron cryo-microscopy. A ribosome-bound Sec61 dimer was only observed in presence of a nascent chain, which could indicate that Sec61 oligomerization is induced by translocation of a nascent chain. We obtained similar results for bacterial ribosome-channel complexes. However, the low-affinity binding site seems to be more abundant in bacterial membranes, which indicates that the prokaryotic equilibrium between low- and high-affinity binding sites is adjusted differently from eukaryotes. 1 We propose a model, in which Sec61 exists in different oligomeric states in the ER membrane. Tetrameric Sec61 provides a high-affinity binding site for ribosomes and is readily occupied in vivo. Monomeric or dimeric Sec61 is accessible for targeting by the SRP pathway, which facilitates the interaction between RNC and free Sec61. After transfer of the nascent chain into the channel and dissociation of SR and SRP, more Sec61 molecules could be recruited to stabilize the interaction with the translating ribosome. A dynamic oligomerization equilibrium of Sec61 is thus the core of a mechanism that would guarantee efficient protein translocation in vivo.

Chemie und Pharmazie - Open Access LMU - Teil 02/02
Consecutive Steps of Nucleoside Triphosphate Hydrolysis Are Driving Transport of Precursor Proteins into the Endoplasmic Reticulum

Chemie und Pharmazie - Open Access LMU - Teil 02/02

Play Episode Listen Later Jan 1, 1992


Wed, 1 Jan 1992 12:00:00 +0100 http://epub.ub.uni-muenchen.de/8692/ http://epub.ub.uni-muenchen.de/8692/1/8692.pdf Klappa, Peter; Müller, Günter; Schlenstedt, Gabriel; Wiech, Hans; Zimmermann, Richard Klappa, Peter; Müller, Günter; Schlenstedt, Gabriel; Wiech, Hans und Zimmermann, Richard (1992): Consecutive Steps of Nucleoside Triphosphate Hydrolysis Are Driving Transport of Precursor Proteins into the Endoplasmic Reticulum. In: Neupert, Walter und Lill, Roland (Hrsg.), Membrane biogenesis and protein targeting. Elsevier: Amsterdam u. a., pp. 137-146.

Fundación Juan March
Membranes and cell Compartments (II): The organization and function of the endoplasmic reticulum

Fundación Juan March

Play Episode Listen Later Feb 20, 1989 75:47


Chemie und Pharmazie - Open Access LMU - Teil 01/02
Import of Small Secretory and Membrane Proteins into the Endoplasmic Reticulum

Chemie und Pharmazie - Open Access LMU - Teil 01/02

Play Episode Listen Later Jan 1, 1988


Fri, 1 Jan 1988 12:00:00 +0100 http://epub.ub.uni-muenchen.de/8575/ http://epub.ub.uni-muenchen.de/8575/1/8575.pdf Zimmermann, Richard; Sagstetter, Maria; Schlenstedt, Gabriel; Wiech, Hans; Kaßeckert, Brigitta; Müller, Günter Kamp, Jos A. F. op den (Hrsg.) (1988): Import of Small Secretory and Membrane Proteins into the Endoplasmic Reticulum. NATO Advanced Study Inst. on New Perspectives in the Dynamics of Assembly of Biomembranes, 24.08.-04.09.1987, Cargèse, Korsica, Frankreich. Chemie und Ph

Chemie und Pharmazie - Open Access LMU - Teil 01/02
Import of honeybee prepromelittin into the endoplasmic reticulum

Chemie und Pharmazie - Open Access LMU - Teil 01/02

Play Episode Listen Later Jan 1, 1988


The import of small precursor proteins, derived from the honeybee secretory protein prepromelittin, into dog pancreas microsomes is independent of signal recognition particle (SRP) and docking protein, but requires that charged amino acids at the amino terminus of the mature part are counterbalanced by amino acids with the opposite charge at the carboxy terminus. The import pathway of such precursor proteins was resolved into two sequential steps: (i) binding of precursors to microsomes, and (ii) insertion of precursors into the membrane. Formation of an intramolecular disulfide bridge within the mature part of these precursor proteins allowed association of the oxidized precursors with the microsomal membrane but reversibly inhibited their membrane insertion. Furthermore, membrane insertion was inhibited by ATP depletion. Different prepromelittin derivatives were found to depend on ATP to varying degrees. We conclude that insertion of prepromelittin-derived precursor proteins into microsomal membranes involves a competent conformation of the precursor proteins and that, in general, this is accomplished with the help of both a cytoplasmic component and ATP.

Chemie und Pharmazie - Open Access LMU - Teil 01/02
Import of Honeybee Prepromelittin into the Endoplasmic Reticulum

Chemie und Pharmazie - Open Access LMU - Teil 01/02

Play Episode Listen Later Jan 1, 1988


Fri, 1 Jan 1988 12:00:00 +0100 http://epub.ub.uni-muenchen.de/8578/ http://epub.ub.uni-muenchen.de/8578/1/8578.pdf Müller, Günter; Zimmermann, Richard Müller, Günter und Zimmermann, Richard (1988): Import of Honeybee Prepromelittin into the Endoplasmic Reticulum. In: Bissel, Mina; Deho, G.; Sironi, G. und Torriani, A. (Hrsg.), Gene expression and regulation. Excerpta Medica: Amsterdam u. a., pp. 199-208. Chemie und Pharmazie

Chemie und Pharmazie - Open Access LMU - Teil 01/02
Import of honeybee prepromelittin into the endoplasmic reticulum

Chemie und Pharmazie - Open Access LMU - Teil 01/02

Play Episode Listen Later Jan 1, 1987


Honeybee prepromelittin is correctly processed and imported by dog pancreas microsomes. Insertion of prepromelittin into microsomal membranes, as assayed by signal sequence removal, does not depend on signal recognition particle (SRP) and docking protein. We addressed the question as to how prepromelittin bypasses the SRP/docking protein system. Hybrid proteins between prepromelittin, or carboxy-terminally truncated derivatives, and the cytoplasmic protein dihydrofolate reductase from mouse were constructed. These hybrid proteins were analysed for membrane insertion and sequestration into microsomes. The results suggest the following: (i) The signal sequence of prepromelittin is capable of interacting with the SRP/docking protein system, but this interaction is not mandatory for membrane insertion; this is related to the small size of prepromelittin. (ii) In prepromelittin a cluster of negatively charged amino acids must be balanced by a cluster of positively charged amino acids in order to allow membrane insertion. (iii) In general, a signal sequence can be sufficient to mediate membrane insertion independently of SRP and docking protein in the case of short precursor proteins; however, the presence and distribution of charged amino acids within the mature part of these precursors can play distinct roles.