Podcasts about G protein

CRNA School Prep Academy Podcast

Play Episode Listen Later Jul 26, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.24.550398v1?rss=1 Authors: Kwon, H., Santhosh, D., Huang, Z. Abstract: Microglia, the resident immune cell of the brain, play critical roles in brain development, function, and disease. However, how microglial activity is regulated in this process remains to be elucidated. Here we report an amyloid precursor protein (APP) and heterotrimeric G protein-mediated pathway that negatively regulates microglial inflammatory activation during cerebral cortex development. Disruption of this pathway results in dysregulated microglial activity, excessive extracellular matrix proteinase production, cortical basement membrane breach, and laminar assembly disruption. We further show that this pathway is activated by amyloid {beta} (A{beta}), the cleavage product of APP that accumulates in large quantities as plaques in the Alzheimer's disease brain. Specifically, we find A{beta} monomers potently suppress inflammatory cytokine transcription and secretion by brain microglia, in an APP and heterotrimeric G protein-dependent manner. These results discover a previously unknown activity of A{beta} as a negative regulator of brain microglia as well as a new pathway that mediates the signal transduction. They shed new light on the cell-cell communication mechanisms that regulate brain immune homeostasis and may facilitate further insight into Alzheimer's disease pathogenesis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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G Protein Pathway Part #2 With PKA: ICU Drugs & Mechanism Of Action

Play Episode Listen Later Jul 5, 2023 23:18

Mastering the complexities of the G Protein Pathway and deciphering the molecular mechanisms of PKA not only equips you to tackle challenging CRNA interview questions with confidence, but it also unveils a simplified understanding of ICU drugs. Welcome back to the second part of our series on G Protein-coupled Receptor Pathways! Today, your host Jenny Finnell takes you on an exciting and simplified journey into the intricate world of protein kinase A (PKA) and its fascinating involvement in critical care drugs. Buckle up because Jenny will be diving deep into the molecular level to uncover the mechanisms of action behind commonly used ICU drugs like epinephrine and norepinephrine. Get ready for a content-heavy episode as Jenny masterfully breaks down the complexities of PKA and its role in the G Protein Pathway. Join us in understanding how critical care drugs work and ace that CRNA interview! Get access to planning tools, mock interviews, valuable CRNA Faculty guidance, and mapped-out courses that have been proven to accelerate your CRNA success! Become a member of CRNA School Prep Academy here! https://www.crnaschoolprepacademy.com/join Book a mock interview, personal statement, resume and more at http://www.NursesTeachNurses.com Join the CSPA email list here! https://www.cspaedu.com/podcast-email Grab the Study Notes for this episode here: https://www.cspaedu.com/ldmbjald Send Jenny an email or make a podcast request!Hello@CRNASchoolPrepAcademy.com

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CaaX-motif adjacent residues control G protein prenylation under suboptimal conditions

New Matter: Inside the Minds of SLAS Scientists

Play Episode Listen Later Jul 4, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.04.547731v1?rss=1 Authors: Tennakoon, M., Thotamune, W., Payton, J. L., Karunarathne, A. Abstract: Prenylation is a universal and irreversible post-translational modification that supports membrane interactions of proteins involved in various cellular processes, including migration, proliferation, and survival. Thus, dysregulation of prenylation contributes to multiple disorders, including cancers, vascular diseases, and neurodegenerative diseases. During prenylation, prenyltransferase enzymes tether metabolically produced isoprenoid lipids to proteins via a thioether linkage. Pharmacological inhibition of the lipid synthesis pathway by statins has long been a therapeutic approach to control hyperlipidemia. Building on our previous finding that statins inhibit membrane association of G protein {gamma} (G{gamma}) in a subtype-dependent manner, we investigated the molecular reasoning for this differential. We examined the prenylation efficacy of carboxy terminus (Ct) mutated G{gamma} in cells exposed to Fluvastatin and prenyl transferase inhibitors and monitored the subcellular localization of fluorescently tagged G{gamma} subunits and their mutants using live-cell confocal imaging. Reversible optogenetic unmasking-masking of Ct residues was used to probe their contribution to the prenylation process and membrane interactions of the prenylated proteins. Our findings suggest that specific Ct residues regulate membrane interactions of the G{gamma} polypeptide statin sensitivity and prenylation efficacy. Our results also show that a few hydrophobic and charged residues at the Ct are crucial determinants of a protein's prenylation ability, especially under suboptimal conditions. Given the cell and tissue-specific expression of different G{gamma} subtypes, our findings explain how and why statins differentially perturb heterotrimeric G protein signaling in specific cells and tissues. Our results may provide molecular reasoning for repurposing statins as Ras oncogene inhibitors and the failure of using prenyltransferase inhibitors in cancer treatment. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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SLAS Europe 2023 | Interviews with Tony B. Award and Student Poster Award Winners

Play Episode Listen Later Jun 12, 2023 25:30

Recorded straight from the SLAS Europe 2023 exhibit hall floor – New Matter host, Hannah Rosen, Ph.D., and SLAS Scientific Director Lesley Mathews, Ph.D., speaks with winners of the Tony B. Award and the Student Poster Award!Congratulations to our winners!(Listed in interview order)Tony B. Travel AwardÁdám Wolf, Ph.D. Student (Óbuda University)Towards robotic laboratory automation Plug & Play: The “LAPP” frameworkMarisa Parra López, Predoctoral Researcher (University of Granada)A multidisciplinary approach for the identification of Tsg101 UEV ligands with potential as novel broad spectrum antiviralsNatalia Karczewska, Research Biologist (Institute of Bioorganic Chemistry, Polish Academy of Sciences)Evaluation of the bioactivity of compounds using Cell Painting assay and alternative High-Content assaysStudent Poster AwardMorgan Dennis, Ph.D. Student (University of Nottingham )How Can Membrane-based Assays Revolutionise Drug Discovery for G Protein-coupled Receptors?Qian Wei, Ph.D. (Oslo University Hospital)High-Throughput Screening of Small Molecules Targeting FoxP3 in Regulatory T Cells for Cancer TreatmentWhat is the Tony B. Travel Award?This annual travel grant program provides funding for the SLAS International Conference and Exhibition and the SLAS Europe Conference and Exhibition for students, graduate students, post-doctoral associates, and junior faculty with less than four years in their first academic appointments. What is the Student Poster Award?Student posters presented during the SLAS International Conference and Exhibition and SLAS Europe Conference and Exhibition are judged on quality and relevance. Student poster presenters are all eligible for the Student Poster Competition, in which the top three posters are recognized. Winners, up to three, receive a cash prize of $500.Visit our Student Resources to learn more about these awards.Stay connected with SLASOnline at www.slas.orgFacebookTwitter @SLAS_OrgLinkedInInstagram @slas_orgYouTubeAbout SLASSLAS (Society for Laboratory Automation and Screening) is an international professional society of academic, industry and government life sciences researchers and the developers and providers of laboratory automation technology. The SLAS mission is to bring together researchers in academia, industry and government to advance life sciences discovery and technolUpcoming SLAS Events: SLAS 2023 Microscales Innovation in Life Sciences Symposium September 14-15, 2023 La Jolla, CA, USA SLAS 2023 Sample Management Symposium October 12-13, 2023 Washington, D.C., USA SLAS 2023 Data Sciences and AI Symposium November 14-15, 2023 Basel, Switzerland SLAS2024 International Conference and Exhibition February 3-7, 2024 Boston, MA, USA

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Biomolecular Condensates defined by Receptor Independent Activator of G protein Signaling: Properties and Regulation

Play Episode Listen Later May 3, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.02.539089v1?rss=1 Authors: Vural, A., Lanier, S. M. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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β-arrestin-dependent and -independent endosomal G protein activation by the vasopressin type 2 receptor

Play Episode Listen Later Apr 2, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.01.535208v1?rss=1 Authors: Daly, C., Guseinov, A. A., Hahn, H., Tikhonova, I., Thomsen, A. R. B., Plouffe, B. Abstract: The vasopressin type 2 receptor (V2R) is an essential GPCR in renal regulation of water homeostasis. Upon stimulation, the V2R activates Gs and Gq/11, which is followed by robust recruitment of {beta}-arrestins and receptor internalization into endosomes. Unlike canonical GPCR signaling, the {beta}-arrestin association with the V2R does not terminate Gs activation, and thus, Gs-mediated signaling is sustained while the receptor is internalized. Here, we demonstrate that this V2R ability to co-interact with G protein/{beta}-arrestin and promote endosomal G protein signaling is not restricted to Gs, but also involves Gq/11. Furthermore, our data implies that {beta}-arrestins potentiate Gs/Gq/11activation at endosomes rather than terminating their signaling. Surprisingly, we found that the V2R internalizes and promote endosomal G protein activation independent of {beta}-arrestins to a minor degree. These new observations challenge the current model of endosomal GPCR signaling and suggest that this event can occur in both {beta}-arrestin-dependent and -independent manners. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Larissas Erfolgsgeschichte

Superhelden Ohne Cape

Play Episode Listen Later Feb 19, 2023

In dieser Woche spreche ich mit Dr. Larissa Neumann über ihre Genesungsgeschichte. Bei ihr wurden Autoantikörper gegen G-Protein gekoppelte Rezeptoren (GPCR) & gegen α1-/ß1-/ß2-adrenerge, M3-/M4-muskarinerge und AT1-Rezeptoren gefunden. Diese Antikörper werden oft auch bei ME/CFS nachgewiesen. Links mentioned in this episode: Larissa Neumann: IG: dr.larissaneumann www.amarevitalita.com Superhelden Ohne Cape: IG: superheldenohnecape superheldenohnecape@yahoo.com This podcast is hosted by ZenCast.fm

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Functional Optimization of Light-Activatable Opto-GPCRs: Illuminating the Importance of the Proximal C-terminus in G-protein Specificity

Play Episode Listen Later Jan 28, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.27.525823v1?rss=1 Authors: Leemann, S., Kleinlogel, S. Abstract: G-protein coupled receptors (GPCRs) are the largest family of human receptors that transmit signals from natural ligands and pharmaceutical drugs into essentially every physiological process. One main characteristic of GPCRs is their ability to specifically couple with different families of G-proteins, thereby triggering specific downstream signaling pathways. While an abundance of structural information is available on GPCR interactions with G-proteins, little is known about the GPCR domains functionally mediating G-protein specificity, in particular the proximal C-terminus, the structure which cannot be predicted with high confidentiality due to its flexibility. In this study, we exploited OptoGPCR chimeras between light-gated GPCRs (opsins) and ligand-gated GCPRs to systematically investigate the involvement of the C-terminus steering G-protein specificity. We employed rhodopsin-beta2-adrenoceptor and melanopsin-mGluR6 chimeras. We discovered a dominant role of the proximal C-terminus, dictating G-protein selectivity in the melanopsin-mGluR6 chimera, whereas it is the intracellular loop 3, which steers G-protein tropism in the rhodopsin-beta2-adrenoceptor. From the functional results and structural predictions, melanopsin and mGluR6 use a different mechanism to bRhod and b2AR to couple to a selective G-protein. Collectively, this work adds knowledge to the GPCR domains mediating G-protein selectivity, ultimately paving the way to optogenetically elicited specific G-protein signaling on demand. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Endometrial adhesion G protein-coupled receptors are dynamically expressed across the menstrual cycle and expression is altered by ovarian stimulation

Play Episode Listen Later Dec 5, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.04.519044v1?rss=1 Authors: Kalakota, N. R., Lemenze, A., George, L., Zhao, Q., Wu, T., Morelli, S. S., Douglas, N. C., Babwah, A. V. Abstract: Ovarian stimulation (OS), utilized for the development of multiple ovarian follicles for IVF, induces supraphysiologic levels of E2 and an early rise in P4 that disrupt endometrial differentiation and decreases implantation rates or result in placental insufficiency and pregnancy complications. To improve pregnancy rates and reduce the risk of pregnancy complications associated with IVF, it is crucial to advance our molecular understanding of the molecular regulation of endometrial differentiation. Previous studies from our laboratory suggest G protein-coupled receptors (GPCRs) are important regulators of endometrial differentiation. To investigate this further, using a retrospective dataset, we identified all GPCRs expressed across the proliferative and secretory phase of the menstrual cycle and found that many members of the adhesion G protein-coupled receptor (ADGR) family are dynamically expressed. For each ADGR subfamily exhibiting differentially-expressed genes across the cycle, their expression was investigated by RT-PCR in the non-pregnant mouse uterus and decidua on E7.5 of pregnancy. For those genes expressed in the E7.5 decidua, their expression was further quantified by qPCR across early mouse pregnancy. The RT-PCR screen revealed expression of 13 ADGRs (4 of the 9 subfamilies) in E7.5 decidua and among these genes, many were differentially expressed between E0.5 and E5.5 or 6.5 and between E5.5 and E6.5. The dynamic expression of the ADGRs across the menstrual cycle and in early mouse pregnancy, suggests these ADGRs are E2- and/or P4-regulated genes. We therefore hypothesized that for these ADGR genes, mRNA expression would be disrupted in an OS cycle. This hypothesis was tested on endometrial biopsies collected in the secretory phase from prospective cohorts of women in natural and OS cycles. Consistent with the retrospective dataset, our data revealed that members of the ADGR gene family are expressed in the secretory phase of the natural menstrual cycle and for the first time, we show that their expression is altered by ovarian stimulation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

G protein-biased LPAR1 agonism promotes prototypic antidepressant effects

Play Episode Listen Later Nov 3, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.02.514841v1?rss=1 Authors: Kajitani, N., Okada-Tsucioka, M., Inoue, A., Miyano, K., Masuda, T., Boku, S., Iwamoto, K., Ohtsuki, S., Uezono, Y., Aoki, J., Takebayashi, M. Abstract: Prototypic antidepressants, such as tricyclic/tetracyclic antidepressants (TCAs), have multiple pharmacological properties and have been considered to be more effective than newer antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), in treating severe depression. However, the molecular mechanisms underlying the high efficacy of TCAs have not been completely understood. Herein, we found that lysophosphatidic acid receptor 1 (LPAR1), a G protein-coupled receptor, mediates the antidepressant effects of amitriptyline, a typical TCA. Amitriptyline directly bound to LPAR1 and activated downstream G protein signaling without affecting {beta}-arrestin signaling, which implied that amitriptyline could act as a G protein-biased agonist of LPAR1. This biased agonism is unique to TCAs and has not been observed in other antidepressants, such as SSRIs. Long-term infusion of mouse hippocampus with 1-oleoyl-2-O-methyl-glycerophosphothionate (OMPT), a potent G protein-biased LPAR1 agonist, induced behavior similar to that induced by antidepressants. In contrast, LPA, a non-biased agonist of LPAR1, induced anxious behavior, indicating that LPAR1 may regulate conflicting emotional behaviors because of the downstream signaling bias. Furthermore, RNA-seq analysis revealed that LPA and OMPT have opposite patterns of gene expression changes in hippocampus. Ingenuity pathway analysis indicated that chronic intrahippocampal administration of OMPT could activate LPAR1 downstream signaling (Rho and MAPK), whereas LPA suppressed LPAR1 signaling. The results reveal the unique antidepressant effects of TCAs and indicate the potential of G protein-biased agonists of LPAR1 as targets for novel antidepressants. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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A subpopulation of peripheral sensory neurons expressing the Mas-related G Protein-Coupled Receptor d (Mrgprd) generates pain hypersensitivity in painful diabetic neuropathy.

Play Episode Listen Later Oct 28, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.27.514066v1?rss=1 Authors: George, D. S., Jayaraj, N. D., Ren, D., Miller, R. E., Malfait, A.-M., Miller, R. J., Menichella, D. M. Abstract: Painful diabetic neuropathy (PDN) is one of the most common and intractable complications of diabetes. PDN is characterized by neuropathic pain accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability, axonal degeneration, and loss of cutaneous innervation. However, the complete molecular profile underlying the hyper-excitable cellular phenotype of DRG nociceptors in PDN has not been elucidated. This gap in our knowledge is a critical barrier to developing effective, mechanism-based, and disease-modifying therapeutic approaches which are urgently needed to relieve the symptoms of PDN. Using single-cell RNA sequencing we demonstrated an increased expression of the Mas-related G Protein- Coupled Receptor d (Mrgprd) in a subpopulation of DRG neurons in the well-established High-Fat Diet (HFD) mouse model of PDN. In vivo calcium imaging allowed us to demonstrate that activation of Mrgprd receptors expressed by cutaneous afferents produced DRG neuron hyper-excitability and oscillatory calcium waves. Furthermore, Mrgprd-positive cutaneous afferents persist in diabetic mice skin. Importantly, limiting Mrgprd signaling or Mrgprd-positive DRG neuron excitability, reversed mechanical allodynia in the HFD mouse model of PDN. Taken together, our data highlights a key role of Mrgprd-mediated DRG neuron excitability in the generation and maintenance of neuropathic pain in a mouse model of PDN. Hence, we propose Mrgprd as a promising accessible target for developing effective therapeutics currently unavailable for treating neuropathic pain in PDN. Furthermore, understanding which DRG neurons cell type is mediating mechanical allodynia in PDN is of fundamental importance to our basic understanding of somatosensation and may provide an important way forward for identifying cell-type-specific therapeutics to optimize neuropathic pain treatment and nerve regeneration in PDN. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Structure of a G protein-coupled receptor with GRK2 and a biased ligand

Psychiatry.dev - All Abstracts TTS

Play Episode Listen Later Oct 19, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.19.512855v1?rss=1 Authors: Duan, J., Liu, H., Ji, Y., Yuan, Q., Li, X., Wu, K., Gao, T., Zhu, S., Jiang, Y., Yin, W., Xu, H. E. Abstract: Phosphorylation of G protein-coupled receptors (GPCR) by GPCR kinases (GRKs) desensitizes G protein signaling and promotes arrestin signaling, which is also modulated by biased ligands. Molecular assembly of GRKs to GPCRs and the basis of GRK-mediated biased signaling remain largely unknown due to the weak GPCR-GRK interactions. Here we report the complex structure of neurotensin receptor 1 (NTSR1) bound to GRK2, Gaq, and an arrestin-biased ligand, SBI-553, at a resolution of 2.92 Angstrom. The high-quality density map reveals the clear arrangement of the intact GRK2 with the receptor, with the N-terminal helix of GRK2 docking into the open cytoplasmic pocket formed by the outward movement of the receptor TM6, analogous of the binding of G protein to the receptor. Strikingly, the arrestin-biased ligand is found at the interface between GRK2 and NTSR1 to enhance GRK2 binding. The binding mode of the biased ligand is compatible with arrestin binding but is clashed with the binding of a G protein, thus provide an unambiguous mechanism for its arrestin-biased signaling capability. Together, our structure provides a solid model for understanding the details of GPCR-GRK interactions and biased signaling. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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G protein-biased GPR3 signaling ameliorates amyloid pathology in a preclinical Alzheimer's disease mouse model – PubMed

Play Episode Listen Later Sep 28, 2022

https://psychiatry.dev/wp-content/uploads/speaker/post-10040.mp3?cb=1664385118.mp3 Playback speed: 0.8x 1x 1.3x 1.6x 2x Download: G protein-biased GPR3 signaling ameliorates amyloid pathology in a preclinical Alzheimer’s disease mouse model – PubMed Yunhong Huang et al. PNAS. 2022.Full EntryG protein-biased GPR3 signaling ameliorates amyloid pathology in a preclinical Alzheimer's disease mouse model – PubMed

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The Tre1/S1pr1 phospholipid-binding G protein-coupled receptor signaling pathway is required for astrocyte morphogenesis

Play Episode Listen Later Sep 17, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.15.508188v1?rss=1 Authors: Chen, J., Stork, T., Kang, Y., Sheehan, A., Paton, C., Monk, K., Freeman, M. Abstract: Astrocytes play crucial roles in regulating neural circuit function by forming a dense network of synapse-associated membrane specializations. Intimate astrocyte-synapse contact is thought to be crucial for astrocyte function, yet signaling pathways regulating astrocyte morphogenesis remain poorly defined. Here we show the Drosophila lipid-binding G protein-coupled receptor (GPCR) Tre1, likely acting through Rac1, is required for astrocytes to elaborate their complex morphologies. The lipid phosphate phosphatases Wunen/Wunen2, which process phospholipid ligands for Tre1, also regulate astrocyte growth, and act upstream of Tre1 as Wunen/Wunen2-mediated astrocyte overgrowth is suppressed by Tre1 loss. Loss of s1pr1, the functional analog of Tre1 in zebrafish, also leads to disruption of astrocyte morphogenesis. Live-imaging and pharmacology demonstrate that S1pr1 balances proper astrocyte process extension/retraction dynamics during morphogenesis, and that S1pr1 signaling is required throughout astrocyte development. Our work identifies lipid-binding GPCRs like Tre1 and S1pr1 as potent evolutionarily conserved regulators of astrocyte morphological complexity. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

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Is Pharmacology Difficult Podcast G PROTEIN COUPLED RECEPTOR-2

Play Episode Listen Later Oct 17, 2021 13:19

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay. As a continuation of yester episode, today i will be discussing the three major effector pathways of G Protein Coupled Receptor , firstly the Adenylyl cyclase enzyme-cAMP pathway, then IP3-DAG Pathway, Ion channel regulation,... All will be explained with apt examples and details! Termination of pathways forms a major notable point to discuss, never to be missed.. Wishing you all a very Happy Sunday!! For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!! You can access various links via - https://linktr.ee/ispharmacologydifficult

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Is Pharmacology Difficult Podcast G PROTEIN COUPLED RECEPTOR-2

Play Episode Listen Later Oct 17, 2021 13:19

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.As a continuation of yester episode, today i will be discussing the three major effector pathways of G Protein Coupled Receptor , firstly the Adenylyl cyclase enzyme-cAMP pathway, then IP3-DAG Pathway, Ion channel regulation,...All will be explained with apt examples and details! Termination of pathways forms a major notable point to discuss, never to be missed.. Wishing you all a very Happy Sunday!! For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!! You can access various links via - https://linktr.ee/ispharmacologydifficult

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Is Pharmacology Difficult Podcast G PROTEIN COUPLED RECEPTOR-2

Play Episode Listen Later Oct 17, 2021 13:19

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.As a continuation of yester episode, today i will be discussing the three major effector pathways of G Protein Coupled Receptor , firstly the Adenylyl cyclase enzyme-cAMP pathway, then IP3-DAG Pathway, Ion channel regulation,...All will be explained with apt examples and details! Termination of pathways forms a major notable point to discuss, never to be missed.. Wishing you all a very Happy Sunday!! For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!! You can access various links via - https://linktr.ee/ispharmacologydifficult

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Is Pharmacology Difficult Podcast G PROTEIN COUPLED RECEPTOR-1

Play Episode Listen Later Oct 9, 2021 11:42

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay. In today's episode I will narrate the famous poem "Windows" by Wes Magee, communicate its amazing message and look into the window of today's topic i.e. G Protein coupled receptors. First and foremost a little word about the receptor nature and types, and then all about G protein coupled receptors, their structure, mechanism introduction and a teaser of upcoming episode too! All in all a good weekend diary to listen to! Hope you all like it........ For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!! You can access various links via https://linktr.ee/ispharmacologydifficult

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Is Pharmacology Difficult Podcast G PROTEIN COUPLED RECEPTOR-1

Play Episode Listen Later Oct 9, 2021 11:42

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.In today's episode I will narrate the famous poem "Windows" by Wes Magee, communicate its amazing message and look into the window of today's topic i.e. G Protein coupled receptors.First and foremost a little word about the receptor nature and types, and then all about G protein coupled receptors, their structure, mechanism introduction and a teaser of upcoming episode too! All in all a good weekend diary to listen to! Hope you all like it........ For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!You can access various links viahttps://linktr.ee/ispharmacologydifficult

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Is Pharmacology Difficult Podcast G PROTEIN COUPLED RECEPTOR-1

The Medbullets Step 1 Podcast

Play Episode Listen Later Oct 9, 2021 11:42

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.In today's episode I will narrate the famous poem "Windows" by Wes Magee, communicate its amazing message and look into the window of today's topic i.e. G Protein coupled receptors.First and foremost a little word about the receptor nature and types, and then all about G protein coupled receptors, their structure, mechanism introduction and a teaser of upcoming episode too! All in all a good weekend diary to listen to! Hope you all like it........ For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!You can access various links viahttps://linktr.ee/ispharmacologydifficult

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Signal Transduction II: G-protein coupled receptors (GPCR)

Metabolism Made Easy

Play Episode Listen Later Jun 3, 2021 34:42

This podcast covers thd mechanism of activation of two GPCRs: The beta- adrenergic and the alpha1-adrenergic receptors. This biochemistry content may be useful to premedical and medical students. --- Send in a voice message: https://anchor.fm/a-j-ghalayini/message

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Reception: G Protein Receptors, Tyrosine Kinase Receptors

My AP Biology Thoughts

Play Episode Listen Later May 25, 2021 5:12

My AP Biology Thoughts Unit 4 Cell Communication and Cell CycleWelcome to My AP Biology Thoughts podcast, my name is Sid and I am your host for episode #86 called Unit 4 Cell Communication and Cell Cycle: G Protein Receptors and Tyrosine Kinase Receptors. Segment 1: Introduction to G protein receptors and tyrosine kinase receptors G Protein receptors and tyrosine kinase receptors both work to mediate cell communication by binding a signaling molecule, which is also called a ligand. Then this signal is sent through a transduction pathway where the last target protein causes some response. The response for both can be a variety of things such as gene expression, apoptosis, metabolic responses, cell division, or cell growth. Despite being similar in this way, g protein receptors and tyrosine kinase receptors work in very different ways Segment 2: More About G protein receptors Let's start by discussing g protein receptors. G proteins are very diverse and can bind to many different signals. One example is odorant (or scent) receptors. G proteins receptors are located in the cell membrane which is where an extracellular ligand binds to it. The signal is eventually sent to a g protein which is located on the membrane, but on the cytoplasmic side. Before the G protein is activated, GDP is bound to it which keeps it inactive. GDP is guanosine diphosphate. After the signal binds to the receptor, the receptor slightly changes shape and becomes active. Then, the GDP binds to the g protein receptor. Since the G protein no longer has a GDP bound to it, it frees it up to accept and bind to GTP. The GTP activates the G protein. The G protein is made up of three subunits: alpha, beta, and gamma. When the GTP is bound to the G protein and activates it, the alpha subunit detaches and moves away from the receptor. Now the G protein is split into two parts: one part is the single alpha subunit and the other is the beta and gamma subunits. These two parts can go on to interact with other proteins and cause a transduction pathway that results in one of many responses. Eventually, the alpha subunit comes back and hydrolyzes the GTP which keeps the G protein active and changes it back into GDP. At this point the G protein will once again become inactive. G proteins coupled receptors are very important in the human body. Disruptions can cause diseases like cystic fibrosis or cholera. Now let's talk about tyrosine kinase receptors. Tyrosine kinase receptors are enzyme linked receptors. Enzyme linked receptors are receptors that are associated with an enzyme. A kinase is a protein that phosphorylates other proteins. For tyrosine kinase receptors, the kinase phosphorylates tyrosine. To start the process, a signalling molecule attaches to two tyrosine kinase receptors. These come together and form a dimer. Then, each tyrosine kinase receptor phosphorylates the domains of the tyrosine kinase receptor. Then, once the tyrosine is phosphorylated, it can send signals to other molecules Segment 3: Connection to the Course G protein receptors and tyrosine kinase receptors are very important to many species. Problems with g protein receptors can cause choler, cystic fibrosis, and some bacterial infections. Problems with tyrosine kinase receptors can also cause diseases and cancers. Both of these receptors play integral parts in many different species. This can be evidence of the endosymbiotic theory. Since so many species use these receptors, they likely came from a common ancestor and had an evolutionary advantage. Thank you for listening to this episode of My AP Biology Thoughts. For more student-ran podcasts and digital content, make sure that you visit http://www.hvspn.com (www.hvspn.com). Music Credits: "Ice Flow" Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 4.0 License http://creativecommons.org/licenses/by/4.0/ Subscribe to our Podcast...

disruption kevin macleod gdp reception music credits enzyme receptors gtp tyrosine ice flow tyrosine kinase g protein

Pharmacology | G Protein-Coupled Receptors (GPCR)

Play Episode Listen Later Apr 30, 2021 23:24

In this episode, we review the high-yield topic of G Protein-Coupled Receptors (GPCR) from the Pharmacology section. --- Send in a voice message: https://anchor.fm/medbulletsstep1/message

coupled pharmacology receptors g protein gpcr

#030 - Happy & High - durch Sport und Drogen? - Wirkung von Endorphinen und Opiaten

BIOLOGO

Play Episode Listen Later Apr 15, 2021 22:55

Unbedingt im Skript mitverfolgen (S. 29/30) Du erfährst... - wie Glücksgefühle beim Runners' High entstehen - wie es zu Abmilderung von Schmerzwahrnehmung kommt - wie Morphin, Opium und Heroin wirken! Fachbegriffe: präsynaptische Hemmung, postsynoptische Hemmung, Dopamin, Endorphin, Heroin, Opium, G-Protein, GTP, GDP, second messenger, cAMP, ATP, Calciumionenkanal, Adenylatzyklase, Silencer, Genexpression, Transkriptionsfaktor, Hypophyse, Nucleus accumbens, Area tegmentalis, sensorisches Neuron, Nozizeptoren, uvm.

camp durch gdp wirkung heroin runners atp drogen unbedingt opium endorphins nucleus neuron skript dopamin silencer morphin gtp fachbegriffe hemmung g protein genexpression hypophyse opiaten

#022 - Adrenalin-Kick oder Koffein-Boost? - Von Transmittern, Synapsen und second messenger-Systemen

BIOLOGO

Play Episode Listen Later Mar 3, 2021 15:50

HIER geht es zum ergänzenden Skript:) Du erfährst: 1) Was Botenstoffe sind... 2) wie sie an einer Synapse wirken... 3) wie Koffein und Adrenalin ein second messenger-System beeinflussen Schreibe gerne Fragen/Feedback/Wünsche an biologopodcast@googlemail.com oder ... @biologopodcast auf Instagram Fachbegriffe der Folge: Transmitter, Hormone, Serotonin, Dopamin, Glutamat, Acetylcholin, Aktionspotential, Endknöpfchen, Calciumkanäle, Transmitter, synaptische Vesikel, präsynaptische und postsynaptische Membran, Acetylcholinesterase, Diffusion, cAMP, ATP, G-Protein, Adenosin, Adrenalin, Koffein, Adenylatcyclase. Viel Erfolg beim Lernen!

camp boost hormones messenger lernen atp serotonin diffusion systemen adrenalin synapse koffein viel erfolg dopamin transmitter synapsen glutamat membran g protein adrenalin kick adenosin acetylcholin vesikel

G-Protein Linked Second Messangers

First Past the Post

Play Episode Listen Later Dec 28, 2020 3:34

This episode covers g-protein linked second messangers!

g protein

A Universal Allosteric Mechanism for G Protein Activation

PaperPlayer biorxiv biochemistry

Play Episode Listen Later Nov 16, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.15.383679v1?rss=1 Authors: Knight, K. M., Ghosh, S., Campbell, S. L., Lefevre, T. J., Olsen, R. H. J., Smrcka, A. V., Valentin, N. H., Yin, G., Vaidehi, N., Dohlman, H. G. Abstract: G proteins play a central role in signal transduction and pharmacology. Signaling is initiated by cell-surface receptors, which promote GTP binding and the dissociation of G from the G{beta}{gamma} subunits. Structural studies have revealed the molecular basis for subunit association with receptors, RGS proteins and downstream effectors. In contrast, the mechanism of subunit dissociation is poorly understood. We used cell signaling assays, MD simulations, biochemistry and structural analysis to identify a conserved network of amino acids that dictates subunit release. In the presence of the terminal phosphate of GTP, a glycine forms a polar network with an arginine and glutamate, putting torsional strain on the subunit binding interface. This "G-R-E motif" secures GTP and, through an allosteric link, discharges the G{beta}{gamma} dimer. Replacement of network residues prevents subunit dissociation, regardless of agonist or GTP binding. These findings reveal the molecular basis for the final committed step of G protein activation. Copy rights belong to original authors. Visit the link for more info

md universal campbell copy replacement olsen activation yin structural mechanism signaling ghosh lefevre gtp rgs biorxiv vaidehi g protein

The single pass membrane protein MRAP2 regulates energy homeostasis by promoting primary cilia localization of the G protein-coupled receptor MC4R

Play Episode Listen Later Nov 15, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.13.382325v1?rss=1 Authors: Bernard, A. A., Ojeda Naharros, I., Bourgain-Guglielmetti, F., Ciprin, J., Yue, X., Zhang, S., McDaid, E., Nachury, M. V., Reiter, J., Vaisse, C. Abstract: The G protein-coupled receptor MC4R (Melanocortin-4 Receptor) and its associated protein MRAP2 (Melanocortin Receptor-Associated Protein 2) are both essential for the regulation of food intake and body weight in humans and mice. MC4R localizes and functions at the neuronal primary cilium, a microtubule-based organelle that senses and relays extracellular signals. Here, we demonstrate that MRAP2 is critical for the ciliary localization and weight-regulating function of MC4R. Our data reveal that GPCR localization to primary cilia can require specific accessory proteins that may not be present in heterologous cell systems. Our findings also demonstrate the essential role of neuronal primary cilia localization of MC4R for adequate control of energy homeostasis and the obesity-promoting effect of genetic disruption of this pathway. Copy rights belong to original authors. Visit the link for more info

energy single pass primary copy promoting zhang coupled reiter localization membrane receptor homeostasis regulates cilia yue biorxiv g protein gpcr mc4r

Synaptic integration by co-localized G protein-coupled receptors in presynaptic terminals

Play Episode Listen Later Nov 12, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.12.362491v1?rss=1 Authors: Church, E., Hamid, E., Zurawski, Z. P., Alford, S. Abstract: Presynaptic terminals have been little studied as sites of synaptic integration because of inaccessibility. Gi/o-mediated presynaptic inhibition is ubiquitous and either reduces release probability (Pr) by inhibiting Ca2+ entry or inhibits directly at SNARE complexes. At CA1-subicular presynapses, 5-HT1B and GABAB receptors colocalize. GABABRs inhibit Ca2+ entry, whereas 5-HT1BRs Ca2+-dependently target SNARE complexes. We demonstrate that GABABRs, alter Pr, but 5-HT1BRs reduce cleft glutamate concentrations allowing strong inhibition of AMPA- but not NMDA-receptor responses. Simulations of glutamate release and receptor binding demonstrates that experimental effects on release and low affinity antagonism are well-fit by reduced release rates. Train-dependent presynaptic Ca2+ accumulation forces frequency-dependent recovery of neurotransmission during 5-HT1BR activation, consistent with competition between Ca2+-synaptotagmin and G{beta}{gamma} at SNARE complexes. Thus, stimulus trains in 5-HT unveil dynamic synaptic modulation and a sophisticated hippocampal output filter, that itself is modulated by colocalized GABABRs which alter presynaptic Ca2+ allowing complex presynaptic integration. Copy rights belong to original authors. Visit the link for more info

pr train integration copy gi coupled snare alford simulations hamid ht localized terminals receptors nmda synaptic ampa biorxiv ca2 g protein gabab

The G protein-Coupled Metabotropic Glutamate Receptor 1 controls neuronal macroautophagy

PaperPlayer biorxiv bioinformatics

Play Episode Listen Later Nov 2, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.02.365783v1?rss=1 Authors: Donoso, M., Speranza, L., Kalinowska, M., Castillo, C., De Sanctis, C., Francesconi, A. Abstract: Autophagy is an evolutionarily conserved, highly regulated catabolic process critical to neuronal homeostasis, function and survival throughout organismal lifespan. However, the external factors and signals that control autophagy in neurons are still poorly understood. Here we report that the G protein-coupled metabotropic glutamate receptor 1 (mGlu1) contributes to control basal autophagy in the brain. Autophagy is upregulated in the brain of adult mGlu1 knockout mice and genetic deletion or pharmacological inhibition of native mGlu1 receptors enhances autophagy flux in neurons. The evolutionarily conserved adaptor protein FEZ1, identified by a genome-wide screen as mGlu1 receptor interacting partner, was found to participate in the regulation of neuronal autophagy and to be required for repression of autophagy flux by the mGlu1 receptor. Furthermore, FEZ1 appears to enable association of mGlu1 with Ulk1, a core component of the autophagy pathway. Thus, we propose that the mGlu1 receptor contributes to restrain constitutive autophagy in neurons. Copy rights belong to original authors. Visit the link for more info

copy castillo controls coupled speranza receptor autophagy neuronal glutamate biorxiv g protein

Functional Microswitches of Mammalian G Protein-Coupled Bitter-Taste Receptors

Play Episode Listen Later Oct 23, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.23.348706v1?rss=1 Authors: Topin, J., Bouysset, C., Kim, Y., Rhyu, M., Fiorucci, S., Golebiowski, J. Abstract: Bitter taste receptors (TAS2Rs) are a poorly understood subgroup of G protein-coupled receptors (GPCR). No experimental structure of these receptors is available and key-residues controlling their function remain mostly unknown. Here, we have identified the functional microswitches that encode agonist sensing and downstream signaling mechanisms within TAS2Rs sequences. We thoroughly re-aligned the amino-acid sequences of the 25 human TAS2Rs considering residue conservations and all the experimental data from the literature as constraints. As a test case, an accurate homology model of TAS2R16 was constructed and examined by site-directed mutagenesis and in vitro functional assays. Conserved motifs acting as microswitches during agonist-sensing and receptor activation were pinpointed by comparison with the current knowledge on class A GPCRs. Unravelling these sequence-function relationships is of utmost importance to streamline how TAS2Rs functions are encrypted in their sequence. Copy rights belong to original authors. Visit the link for more info

taste copy bitter functional coupled unravelling receptors mammalian biorxiv conserved g protein gpcr fiorucci gpcrs

Activation of G-protein coupled receptors is thermodynamically linked to lipid solvation

PaperPlayer biorxiv biophysics

Play Episode Listen Later Aug 21, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.20.259077v1?rss=1 Authors: Leonard, A. N., Lyman, E. Abstract: Preferential lipid solvation of the G-protein coupled A2A adenosine receptor (A2AR) is evaluated from 35 sec of all-atom molecular dynamics simulation. A coarse-grained transition matrix algorithm is developed to overcome slow equilibration of the first solvation shell, obtaining statistically robust estimates of the free energy of solvation by different lipids for the receptor in different activation states. Results indicate preference for solvation by unsaturated chains, which favors the active receptor. A model for lipid-dependent GPCR activity is proposed in which the chemical potential of lipids in the bulk membrane modulates receptor activity. The enthalpy and entropy associated with moving saturated vs. unsaturated lipids from bulk to A2AR's first solvation shell are compared. In the simulated mixture, saturated chains are disordered (i.e., obtain a favorable entropic contribution) when partitioning to the receptor surface, but this is outweighed by a favorable enthalpic contribution for unsaturated chains to occupy the first solvation shell. Copy rights belong to original authors. Visit the link for more info

results copy activation coupled lyman lipids receptors a2a biorxiv g protein gpcr

Routine sub-2.5 A cryo-EM structure determination of B-family G protein-coupled receptors

PaperPlayer biorxiv biophysics

Play Episode Listen Later Aug 21, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.21.260851v1?rss=1 Authors: Danev, R., Belousoff, M., Liang, Y.-L., Zhang, X., Wootten, D., Sexton, P. M. Abstract: Cryo-electron microscopy (cryo-EM) experienced game-changing hardware and software advances about a decade ago. Since then, there have been gradual and steady improvements in experimental and data analysis methods. Nonetheless, structural analysis of nonsymmetric membrane proteins, such as G protein-coupled receptors (GPCRs), remains challenging. Their relatively low molecular weight and obstruction by the micelle/nanodisc result in marginal signal levels, which combined with the intrinsic flexibility of such complexes creates difficult structural study scenarios. Pushing the performance limits of cryo-EM requires careful optimization of all experimental aspects. To this end, it is necessary to build quantitative knowledge of the effect each parameter has on the outcome. Here, we present in-depth analysis of the influence of the main cryo-EM experimental factors on the performance for GPCR structure determination. We used a tandem experiment approach that combined real-world structural studies with parameter testing. We quantified the effects of using a Volta phase plate, zero-loss energy filtering, objective lens aperture, defocus magnitude, total exposure, and grid type. Through such systematic optimization of the experimental conditions, it has been possible to routinely determine class B1 GPCR structures at resolutions better than 2.5 A. The improved fidelity of such maps helps to build higher confidence atomic models and will be crucial for the future expansion of cryo-EM into the structure-based drug design domain. The optimization guidelines drafted here are not limited to GPCRs and can be applied directly for the study of other challenging membrane protein targets. Copy rights belong to original authors. Visit the link for more info

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Distinct specificity of two pheromone G-protein coupled receptors, Map3 and Mam2, in fission yeast species.

PaperPlayer biorxiv genetics

Play Episode Listen Later Jul 22, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.22.215566v1?rss=1 Authors: Seike, T., Sakata, N., Shimoda, C., Niki, H., Furusawa, C. Abstract: Most sexually reproducing organisms have the ability to recognize individuals of the same species. In ascomycetes including yeasts, potential mating between cells of opposite mating-type depends on the molecular recognition of two peptidyl mating pheromones by their corresponding G-protein coupled receptors (GPCRs). Although such pheromone/receptor systems are likely to function in both mate choice and prezygotic isolation, very few studies have focus on the differences in pheromone/receptor system between mating types. The fission yeast Schizosaccharomyces pombe has two mating types (sexes), Plus (P) and Minus (M). Here we investigated the specificity of the two GPCRs, Mam2 and Map3, for their respective pheromones, P-factor and M-factor, in fission yeast. First, we switched GPCRs between S. pombe and the closely related species Schizosaccharomyces octosporus, which showed that SoMam2 (Mam2 of S. octosporus) is partially functional in S. pombe, whereas SoMap3 (Map3 of S. octosporus) is not interchangeable. Next, we swapped individual domains of Mam2 and Map3 with the respective domains in SoMam2 and SoMap3, which revealed differences between the receptors both in the intracellular regions that regulate the downstream signaling of pheromones and in the molecular recognition for pheromone binding. In particular, we demonstrated that two amino acid residues of Map3, F214 and F215, are essential for the specificity of M-factor recognition. Thus, the differences in these two GPCRs are likely to reflect the significantly distinct specificities of their respective pheromone/receptor systems; that is, the specificity of Map3 is more stringent than that of Mam2. We speculate that this sexual asymmetry might allow ascomycete fungi to generate novel prezygotic barriers within a population, while maintaining strong mate choice. Our genetic analyses also contribute to our understanding of the receptors that comprise the Class D GPCRs belonging to the fungal pheromone receptor family. Author summaryCourtship signals play a key role in the fertilization processes of living beings from animals to microorganisms and, in particular, sex pheromones are involved in differentiating among species. On the other hand, changes in a pheromone/receptor system might also alter species-specificity during the selection of a mating partner, which is likely to facilitate prezygotic isolation. Here we demonstrate a distinct difference in the specificity of GPCRs for pheromones between cells of opposite mating-type in the fission yeast Schizosaccharomyces pombe, by conducting a comprehensive genetic analysis and comparison of these proteins between closely related fission yeast species. Our finding of sexual asymmetry due to the relative strictness of receptors in S. pombe suggests that it might be one of the driving forces behind the formation of new species. Such differences in pheromone/receptor interactions between the sexes may occur in a variety of life-forms such as insects and amphibians; hence, the findings of this study might be extended to other organisms. In addition, this study of S. pombe pheromone receptors sheds light on the functions of the unique Class D GPCRs. Copy rights belong to original authors. Visit the link for more info

copy species yeast coupled distinct specificity fission receptors pheromone biorxiv shimoda g protein gpcrs

Suppression of pyramidal neuron G protein-gated inwardly rectifying K+ channel signaling impairs prelimbic cortical function and underlies stress-induced deficits in cognitive flexibility

MedFlashGo | 4 Minutes Or Less Daily Rapid Review Of USMLE, COMLEX, And Shelf For Medical Students

Play Episode Listen Later Jun 8, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.08.139725v1?rss=1 Authors: Anderson, E., Loke, S., Wrucke, B., Engelhardt, A., Hess, E., Hearing, M. Abstract: Background: Imbalance in prefrontal cortical (PFC) pyramidal neuron excitation:inhibition is thought to underlie symptomologies shared across stress-related disorders and neuropsychiatric disease, including dysregulation of emotion and cognitive function. G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels mediate excitability of medial PFC pyramidal neurons, however the functional role of these channels in mPFC-dependent regulation of affect, cognition, and cortical dynamics is unknown. Methods: In mice harboring a floxed version of the kcnj3 (Girk1) gene, we used a viral-cre approach to disrupt GIRK1-containing channel expression in pyramidal neurons within the prelimbic (PL) or infralimbic (IL) cortices. Additional studies used a novel model of chronic unpredictable stress (CUS) to determine the impact on PL GIRK-dependent signaling and cognitive function. Results: In males, loss of pyramidal GIRK-dependent signaling in the PL, but not IL, differentially impacted measures of affect and motivation, and impaired working memory and cognitive flexibility. CUS produced similar deficits in affect and cognition that paralleled a reduction in PL pyramidal GIRK-dependent signaling akin to viral approaches. Viral- and stress-induced behavioral deficits were rescued by systemic injection of a novel, GIRK1-selective agonist, ML-297. Unexpectedly, neither ablation of PL GIRK-dependent signaling or exposure to the CUS regimen impacted affect or cognition in female mice. Conclusions: GIRK-dependent signaling in male mice, but not females, is critical for maintaining optimal PL function and behavioral control. Disruption of this inhibition may underlie stress-related dysfunction of the PL and represent a therapeutic target for treating stress-induced deficits in affect regulation and impaired cognition that reduce quality of life. Copy rights belong to original authors. Visit the link for more info

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#12 G protein receptors and Bladder Dysfunction | Biochemistry | MedFlashGo Question Of The Day

Play Episode Listen Later Feb 12, 2020 4:01

Welcome To The MedFlashGo Podcast. This Is Your Daily 4 Minutes Or Less Rapid Review For USMLE, COMLEX, And Shelf Exams. We release a new episode every weekday! In this question of the day, Sean asks students to identify the correct G protein receptor based on the given characteristics described. These questions are powered by MedFlashGo The First Voice-based interactive medical question bank currently available on Alexa. This tool allows medical students to study medical topics and be interactively tested without the use of a screen. You can study on your couch, in your car, and on the move without the use of a screen. To get access to your 50 free questions go on to your Alexa application and search medflashgo In the skills section. To learn more details go to medflashgo.com and check out our frequently asked questions section. Please know that these questions were creatively designed by medical students and physicians for the purpose of education and do not replace health information given from your health professionals. We have tried our best to make sure the information is accurate please, so please let us know if you find any errors and we will be sure to correct them. --- Send in a voice message: https://anchor.fm/medflashgo/message

dysfunction biochemistry bladder question of the day receptors g protein comlex

Circulation February 28, 2017

Circulation on the Run

Play Episode Listen Later Feb 27, 2017

Dr. Carolyn L.: Welcome to Circulation on the Run, your weekly podcast, summary, and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. On our podcast today we are discussing the role of diastolic stress testing and the evaluation of heart failure with preserved dejection fraction, a really hot topic indeed, but first here's your summary of this week's issue. The first study tackles the obesity paradox in cardiac surgery, where morbidity and mortality are lower in obese patients. This study sought to ask the question, "Is this due to reverse epidemiology, bias, or confounding?" To answer this question, Dr. Maris Kelko and colleagues from University Leicester in United Kingdom used two separate analysis. One, registry data from the National Adult Cardiac Surgery Registry and two, a systematic review in meta-analysis of studies. Of more than 400,000 patients in the cohort study and more than 550,000 patients in the systematic review, the authors found a U shape association between mortality and body mass index classes, where lower mortality was observed in overweight and obese class one and two patients, relative to normal weight patients, and mortality was increased in underweight individuals. Now, the obesity paradox has been attributed to reverse epidemiology where the survival benefit associated with obesity is thought to actually reflect worse outcomes in the underweight patients who also had frailty, cachexia, or severe chronic disease. However, in the current study, counter to the reverse epidemiology hypothesis, the protective effects of obesity were less in patients with chronic renal, lung, or cardiac disease and greater in older patients as well as in those with complications of obesity, such as metabolic syndrome and atherosclerosis. Furthermore, adjustments for important confounders did not alter the results. The authors therefore concluded that obesity is associated with lower risks after cardiac surgery with consistent effects noted in multiple analysis even after attempting to address residual confounding and reverse causation. The authors even went as far as to suggest that their findings do not support common practice where weight loss is recommended prior to surgery or where very obese patients are refused surgery in the morbidly obese. These provocative findings are discussed in an accompanying editorial by Doctor's Carnethon and Kahn from Northwestern University. While the editorialists agree that this well-designed study highlights an important knowledge gap, they pointed out that the obese class two patients had nearly five times greater risk for deep sternal wound infection and 25% higher likelihood of needing renal replacement therapy. In such patients additional intervention in the perioperative period may still be indicated and include weight loss recommendations and postoperative surveillance for complications. Thus, a more cautious final recommendation may be for future studies to prospectively assess weight loss interventions prior to elective surgery in the context of overall surgical risk as assessed by the EuroSCORE or STS models. The next paper describes mechanistic studies showing for the first time that nucleoside diphosphate kinase suppresses cyclic-AMP formation in human heart failure. In this paper by First Authors, Dr. Abu Taha and Hagemann, corresponding authors Dr.'s Tobref and Weilend from the Heidelberg University in Germany, the authors performed biochemical studies of nucleoside diphosphate kinase and G Protein signaling in human and rat tissue samples, assessed the functional impact of nucleoside diphosphate kinase C on cyclic-AMP levels and contractility and isolated red cardiomyocytes and determined that in vitro effects of these nucleoside diphosphate kinases on contractility in zebra, fish and mice. They identified nucleoside diphosphate kinase as the critical isoform for the regulation of G Protein function and cyclic-AMP levels in the heart with important consequences for cardiac contractility. The increased nucleoside diphosphate kinase membrane content in human heart failure could potentially counteract a fading beta adrenoceptor response in the early stages of heart failure by increasing the amount of G Alpha stimulatory proteins in the plasma membrane. However, by switching from stimulatory to G Alpha inhibitory to activation, nucleoside diphosphate kinase may play a role in heart failure progression by reducing cyclic-AMP levels, typical for end-stage human heart failure. The study, therefore contributes to a better understanding of the molecular processes, underlying alter G Protein signaling in heart failure, and may help to develop new heart failure therapies. The next study tested the hypothesis, that high intensity interval training is superior to moderate continuous training in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure and reduced ejection fraction. Doctor Ellingson and colleagues from the Norwegian University of Science and Technology, performed a multicenter trial, comparing twelve weeks of supervised interventions of high-intensity interval training at 90 to 95% maximal heart rate, moderate continuous training at 60 to 70% maximal heart rate, or a recommendation of regular exercise in 261 patients with heart failure and ejection fraction less than 35%, in New York Heart Association class II or III status. The primary end point of change in left ventricular end-diastolic diameter from baseline to twelve weeks was not different between the high-intensity and moderate continuous groups. There was also no difference between the high-intensity and moderate groups in peak oxygen uptake, although both were superior to the recommendation for regular exercise. None of these changes were maintained at follow up after 52 weeks. Serious adverse events were not statistically different. However, training records showed that 51% of patients exercised below the prescribed target, during supervised high-intensity interval training, and 80% above the recommended target in those with moderate continuous training. Given that high-intensity interval training was not superior to moderate continuous training, in reversing remodeling or improving secondary end points, and considering that adherence to the prescribed exercise intensity based on heart rate was difficult to achieve even in the supervised setting. The authors concluded that moderate continuous training remains the standard exercise modality for patients with chronic heart failure. The final paper tells us, that brain emboli after left ventricular endocardial ablation may be more common than we knew. First author Doctor Whitman, corresponding author Doctor Marcus and colleagues from University of California studied eighteen consecutive patients, scheduled for ventricular tachycardia or premature ventricular contraction ablation, over a nine month period. Twelve patients undergoing left ventricular ablation were compared to a control group of six patients, undergoing right ventricular ablation only. Heparin was administrated with a goal activated clotting time of 300 to 400 seconds for all left ventricular procedures. Pre impulse procedural brain magnetic resonance imaging was performed on each patient within a week of the ablation procedure. The authors found that seven of the twelve patients, or 58% undergoing left ventricular ablation, experienced a total of sixteen cerebral emboli, compared with none among patients undergoing right ventricular ablation. Seven of the eleven patients undergoing a retrograde approach to the left ventricle, developed at least one new brain lesion. Thus, more than half of patients undergoing routine left ventricular ablation procedures, experienced new brain emboli after the procedure, even in the absence of clinically apparent stroke. Future research is critical to understanding the long-term consequences of these lesions and to determine optimal strategies to avoid them. This is further discussed in an editorial entitled "The Sound of Silence". How much noise should we make about post ablation silence strokes? By Doctor Z and Vora from Stanford University. Well, those were your summaries, now for our featured discussion. I am so thrilled to have with me two special guests to discuss the topic of the diagnosis of heart failure preserved ejection fraction or HFpEF. As you all know, that's my favorite topic and I have favorite people with me today. First, the corresponding author of our feature paper, Doctor Barry Borlaug from Mayo Clinic, Rochester, Minnesota. And, for the first time on the podcast, Doctor Mark Drazner, Senior Associate Editor from UT Southwestern. So, welcome Barry and Mark. Barry Borlaug: Thank you Carolyn. Mark Drazner: Thank you, great to be here. Dr. Carolyn L.: So, Barry, you talked about the role of stress diastolic testing, shall I call it, in the diagnosis of HFpEF in your paper. Could you tell us why you looked at it and what you found? Barry Borlaug: Sure, Carolyn. When you have dyspnea and fatigue and you got a low EF, it's pretty easy to make the diagnosis of heart failure reduced EF, but we've been struggling for years with making the diagnosis of dyspnea, whether it's HFpEF or not in people with normal ejection fraction. And that's because physical and laboratory and clinical signs of high filling pressures and congestion, are either difficult to see or only present during stress, like physical exercise, in patients. So that's really what motivated us to pursue this study. We took patients, that were referred to our cath lab for invasive hemodynamic exercise testing, so we directly measured filling pressures, PA pressures and cardiac output reserve, to get a gold standard assessment, whether people have heart failure or not. And then we performed simultaneous echocardiography and blood testing to measure NT-proBNP levels, and then we just looked at what we could figure out. Can you accurately discern HFpEF patients from patients without cardiac dyspnea, using these non invasive estimates. We saw that a lot of people, with, for example, NT-proBNP levels that are low enough to be where most would consider HFpEF excluded, actually had HFpEF. And we saw that there were modest correlations between non-invasive echocardiographic estimates of filling pressures, specifically the E to E Prime ratio, and directly measured left heart filling pressures. But when we applied the criteria that had been initially proposed, we saw poor sensitivity to make the diagnosis with exercise. And this was largely related to the difficulty with getting all of the different echocardiographic indices, that are currently examined as part of the diastolic stress testing non-invasively. Next, we looked at just adding the exercise E to E Prime, which is an estimate of filling pressures, and when we used the cut-point, that's already been proposed, according to contemporary data, we found that this substantially improved the sensitivity to identify HFpEF, but there was a bit of a trade-off in that specificity decrease. Dr. Carolyn L.: That's so cool. So let me summarize some of these take-home messages here. First of all, using just rest echo. I was really impressed to see that rest echo indices alone only identifies a third to maybe up to 60% of the patients you found with invasively proven HFpEF. So, we may be specific, but we're really missing quite a number of patients. And then if you exercise them, what your data is really showing is that it's better to exercise them and use this data for the negative predictive value, isn't that what you're saying? Barry Borlaug: You know, the exercise is really the gold standard, so it gives you both, the negative and positive. With the echocardiography, relying on the exercise E to E Prime ratio, that was really helping us, as you say, Carolyn, with the higher negative predictive value. So most people, that had HFpEF, in this series, where we could get adequate, highly controlled environments, adequate diagnostic echocardiographic data, most people that ended up having HFpEF fit those criteria, we could see an elevation in this E to E Prime on exercise, so it did provide good negative predictive value. Dr. Carolyn L.: These are just such important data, because I think we're all still struggling with how to make this diagnosis of HFpEF. Mark, could you just share some thoughts on whether you think this is going to really change practice, even change guidelines? Mark Drazner: I think, if you read this paper, you would recognize it, that it's certainly a critical question that we're all facing, how to make the diagnosis of HFpEF. And all of their guidelines that have been advocated, there really wasn't much data, and these really are the best data out there. So, certainly, it's [inaudible 00:15:41] me a direction of changing practices. Barry says, certainly, the approach will need to be validated, I think, before it reaches high level guidelines, but certainly I think it's a step in the right direction, and points the way towards the future in terms of improving our ability to diagnose HFpEF. And really, that's why both reviewers and [inaudible 00:15:59] this is such an important paper. Dr. Carolyn L.: Right. Barry, I have a quick question for you though. Doing exercise echo, not easy. E to E Primes are all over the place usually. How easy was it? How feasible was this test? Barry Borlaug: So, first I'd like to say that we have outstanding, very well-trained, very highly skilled research scenographers, here at Mayo doing this. In very controlled environment, we're providing plenty of time for them to obtain images and that's going to be a question moving forward, because not everybody in clinical practice has that capability. But with that said, in this very controlled environments, skilled scenographers, we were able to measure the exercise data during low level exercise about 85 to 90% of the time and at peak exercise about 75 to 80% of the time. So, it's fairly feasible, but even in this best case scenario, we can't get it on everybody. Mark Drazner: Even in the [inaudible 00:19:49] echo lab, the recommended approach by the ASE with the four measures. How many times they were not able to acquire all those images, are necessary for those four techniques and so, here you have a [inaudible 00:20:03] of AS echo lab not being able to do that, and being transparent about that, and [inaudible 00:20:08] to the community, saying that, although these are ideal measures, even the [inaudible 00:20:12] perhaps you can't acquire them. I think that was another important point that came out of this and then lead to the focus on the E to E Prime. Barry Borlaug: I couldn't agree more. You got one of the world renowned labs, very skilled scenographers doing imaging, and we're still not able to get it all in each patient, and that just points to the difficulty of getting really high quality diagnostic images, and a lot of time you need the next level test, when that happens. And invasive exercise testing is really that test, the gold standard. Mark Drazner: When you get echos from the outside and you look at the E to E Primes, are you confident that the data, that's generally acquired, is gonna be acceptable for this [inaudible 00:20:50]? Barry Borlaug: Yes and no, I mean I'm always a little bit concerned, but it's not just being a control freak, you know, wanting to see everything, but I think that if it's a still frame doppler, tissue doppler spectrum, you can see that the sample volume is in the right place, and it's really unequivocally normal or abnormal, I feel pretty good about that. Not as good as when they get a full dedicated study here. Mark Drazner: Of course, the gold standard is also difficult. The invasive measurement. Barry Borlaug: Yes it is, I didn't [inaudible 00:21:18] that, but we've been doing a lot of invasive exercise tests for the last ten years now. And we do like 250 a year here, so we're really quite [inaudible 00:21:28] but we have all hands on deck in the lab. We have a couple technicians running gas samples around, all over the place. Somebody is on the medgraphics card, measuring oxygen consumption. We've got a nurse in there, that's helping out, so it's complicated, and of course we're using the micromanometer catheters for the pressure assessments, because you get so much more artifacts from width and under damping and over damping with the pressure tracing, so that's also not easy to do if you say. Mark Drazner: So maybe for practicing cardiologists it's gonna be hard to duplicate that and perhaps spend the energy in terms of doing the exercise echo techniques off the speed, for example. Perhaps, it's another message. Barry Borlaug: I would agree completely. And I think that again, when you do that, if you do a really high quality exercise echo and it's still not quite definitive, then you can refer on to a center that does have that capability, because obviously it's just reality, not everybody is going to be able to do this. Not every place has the size and resources to be able to do these really advanced tasks. Dr. Carolyn L.: And do you apply exercise echo now in making your diagnosis? How do you use this data, for yourself, clinically? Barry Borlaug: We started to think about this, and I think that the best case scenario where the people, that really have an intermediate pretest probability, based on their clinical characteristics. Somebody has jugular distension and a very high NT-proBNP level, and edema, you really don't need further testing, you know that that's going to be HFpEF. And if somebody has no risk factors, and everything is stone cold normal, they don't. But in some of these people that have some signals, but they don't quite meet criteria, we are doing this, again, if they have adequate echocardiographic images at rest. And then we're looking really carefully at the exercise echocardiography data, one concern from this data, I want to make sure people are very circumspect and really critically looking at the quality of their data, because we shouldn't over-interpret equivocal findings. And as you said earlier, E to E Primes can be all over the map, they're very difficult to obtain during exercise. But I think that if everything looks very high quality and is definitely abnormal or definitely normal, that can be helpful. More so, if it's normal. We did see more false positive, so if it is abnormal, we did suggest that you may want to perform further confirmatory testing, because of the higher false positive rate with exercise echo. Mark Drazner: I would say for the listeners, they should take a look at his figure six, which really is a nice diagnostic algorithm, where Barry shows, or advocates, for taking patients with intermediate probability and then using this to restratify that, using [inaudible 00:19:40] approach. I know that, that figure resonated with the editors and the reviewers dramatically, so I'd encourage listeners to take a look at that. Dr. Carolyn L.: Listeners, you heard it right. [inaudible 00:22:36] Circulation on the Run. Don't forget to tell all your friends about this podcast and tune in next week.

university california science technology future germany sound doctors united kingdom minnesota silence run singapore mayo stanford university twelve rochester northwestern university mayo clinic kahn ef whitman circulation sts vora ase norwegian university ut southwestern ellingson hagemann heidelberg university heparin hfpef senior associate editor e prime duke national university nt probnp g protein carolyn lam new york heart association

2b. How Adrenaline Signaling Works (G-Protein Coupled Receptors Part 1)

Play Episode Listen Later Jan 8, 2016 23:55

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2b. How Adrenaline Signaling Works (G-Protein Coupled Receptors Part 1)

Play Episode Listen Later Jan 8, 2016 23:56

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2c. How Sight, Smell, and Taste Work (G-Protein Coupled Receptors Part 2)

Play Episode Listen Later Jan 8, 2016 24:23

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2c. How Sight, Smell, and Taste Work (G-Protein Coupled Receptors Part 2)