TRPC5 Does Not Cause Or Aggravate Glomerular Disease
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TRPC5 Regulates Axonal Outgrowth in Developing Retinal Ganglion Cells
Laboratory Investigation (2020) 100:297–310 https://doi.org/10.1038/s41374-019-0347-1 ARTICLE TRPC5 regulates axonal outgrowth in developing retinal ganglion cells 1 1 2 1 1 Mai Oda ● Hanako Yamamoto ● Hidetaka Matsumoto ● Yasuki Ishizaki ● Koji Shibasaki Received: 22 July 2019 / Revised: 15 November 2019 / Accepted: 15 November 2019 / Published online: 16 December 2019 © The Author(s), under exclusive licence to United States and Canadian Academy of Pathology 2019 Abstract The TRPC5 ion channel is activated upon depletion of intracellular calcium stores, as well as by various stimuli such as nitric oxide (NO), membrane stretch, and cold temperatures. TRPC5 is abundantly expressed in the central nervous system where it has important neuronal functions. In the chick retina, TRPC5 expression was shown to be restricted to amacrine cells (ACs) and Müller glial cells, although its expression was also observed in the ganglion cell layer (GCL) in displaced ACs, as determined by their characteristic cell morphology. However, it is possible that this expression analysis alone might be insufficient to fully understand the expression of TRPC5 in retinal ganglion cells (RGCs). Hence, we analyzed TRPC5 expression by in situ hybridization and immunostaining in the developing mouse retina, and for the first time identified that 1234567890();,: 1234567890();,: developing and mature RGCs strongly express TRPC5. The expression begins at E14.5, and is restricted to ACs and RGCs. It was reported that TRPC5 negatively regulates axonal outgrowth in hippocampal neurons. We thus hypothesized that TRPC5 might have similar functions in RGCs since they extend very long axons toward the brain, and this characteristic significantly differs from other retinal cell types. -
TRPC1 Regulates the Activity of a Voltage-Dependent Nonselective Cation Current in Hippocampal CA1 Neurons
cells Article TRPC1 Regulates the Activity of a Voltage-Dependent Nonselective Cation Current in Hippocampal CA1 Neurons 1, 1 1,2 1,3, Frauke Kepura y, Eva Braun , Alexander Dietrich and Tim D. Plant * 1 Pharmakologisches Institut, BPC-Marburg, Fachbereich Medizin, Philipps-Universität Marburg, Karl-von-Frisch-Straße 2, 35043 Marburg, Germany; [email protected] (F.K.); braune@staff.uni-marburg.de (E.B.); [email protected] (A.D.) 2 Walther-Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, 80336 München, Germany 3 Center for Mind, Brain and Behavior, Philipps-Universität Marburg, 35032 Marburg, Germany * Correspondence: plant@staff.uni-marburg.de; Tel.: +49-6421-28-65038 Present address: Institut für Bodenkunde und Pflanzenernährung/Institut für angewandte Ökologie, y Hochschule Geisenheim University, Von-Lade-Str. 1, 65366 Geisenheim, Germany. Received: 27 November 2019; Accepted: 14 February 2020; Published: 18 February 2020 Abstract: The cation channel subunit TRPC1 is strongly expressed in central neurons including neurons in the CA1 region of the hippocampus where it forms complexes with TRPC4 and TRPC5. To investigate the functional role of TRPC1 in these neurons and in channel function, we compared current responses to group I metabotropic glutamate receptor (mGluR I) activation and looked +/+ / for major differences in dendritic morphology in neurons from TRPC1 and TRPC1− − mice. mGluR I stimulation resulted in the activation of a voltage-dependent nonselective cation current in both genotypes. Deletion of TRPC1 resulted in a modification of the shape of the current-voltage relationship, leading to an inward current increase. In current clamp recordings, the percentage of neurons that responded to depolarization in the presence of an mGluR I agonist with a plateau / potential was increased in TRPC1− − mice. -
TRP CHANNELS AS THERAPEUTIC TARGETS TRP CHANNELS AS THERAPEUTIC TARGETS from Basic Science to Clinical Use
TRP CHANNELS AS THERAPEUTIC TARGETS TRP CHANNELS AS THERAPEUTIC TARGETS From Basic Science to Clinical Use Edited by ARPAD SZALLASI MD, PHD Department of Pathology, Monmouth Medical Center, Long Branch, NJ, USA AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 125 London Wall, London, EC2Y 5AS, UK 525 B Street, Suite 1800, San Diego, CA 92101-4495, USA 225 Wyman Street, Waltham, MA 02451, USA The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK First published 2015 Copyright © 2015 Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangement with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. -
Snapshot: Mammalian TRP Channels David E
SnapShot: Mammalian TRP Channels David E. Clapham HHMI, Children’s Hospital, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA TRP Activators Inhibitors Putative Interacting Proteins Proposed Functions Activation potentiated by PLC pathways Gd, La TRPC4, TRPC5, calmodulin, TRPC3, Homodimer is a purported stretch-sensitive ion channel; form C1 TRPP1, IP3Rs, caveolin-1, PMCA heteromeric ion channels with TRPC4 or TRPC5 in neurons -/- Pheromone receptor mechanism? Calmodulin, IP3R3, Enkurin, TRPC6 TRPC2 mice respond abnormally to urine-based olfactory C2 cues; pheromone sensing 2+ Diacylglycerol, [Ca ]I, activation potentiated BTP2, flufenamate, Gd, La TRPC1, calmodulin, PLCβ, PLCγ, IP3R, Potential role in vasoregulation and airway regulation C3 by PLC pathways RyR, SERCA, caveolin-1, αSNAP, NCX1 La (100 µM), calmidazolium, activation [Ca2+] , 2-APB, niflumic acid, TRPC1, TRPC5, calmodulin, PLCβ, TRPC4-/- mice have abnormalities in endothelial-based vessel C4 i potentiated by PLC pathways DIDS, La (mM) NHERF1, IP3R permeability La (100 µM), activation potentiated by PLC 2-APB, flufenamate, La (mM) TRPC1, TRPC4, calmodulin, PLCβ, No phenotype yet reported in TRPC5-/- mice; potentially C5 pathways, nitric oxide NHERF1/2, ZO-1, IP3R regulates growth cones and neurite extension 2+ Diacylglycerol, [Ca ]I, 20-HETE, activation 2-APB, amiloride, Cd, La, Gd Calmodulin, TRPC3, TRPC7, FKBP12 Missense mutation in human focal segmental glomerulo- C6 potentiated by PLC pathways sclerosis (FSGS); abnormal vasoregulation in TRPC6-/- -
Involvement of TRPC4 and 5 Channels in Persistent Firing in Hippocampal CA1 Pyramidal Cells
cells Article Involvement of TRPC4 and 5 Channels in Persistent Firing in Hippocampal CA1 Pyramidal Cells Alberto Arboit 1,2,3, Antonio Reboreda 1,4 and Motoharu Yoshida 1,3,4,5,* 1 German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany; [email protected] (A.A.); [email protected] (A.R.) 2 Otto-von-Guericke University, 39120 Magdeburg, Germany 3 Faculty of Psychology, Ruhr University Bochum (RUB), Universitätsstraße 150, 44801 Bochum, Germany 4 Leibniz Institute for Neurobiology (LIN), 39118 Magdeburg, Germany 5 Center for Behavioral Brain Sciences (CBBS), 39106 Magdeburg, Germany * Correspondence: [email protected] Received: 1 December 2019; Accepted: 1 February 2020; Published: 5 February 2020 Abstract: Persistent neural activity has been observed in vivo during working memory tasks, and supports short-term (up to tens of seconds) retention of information. While synaptic and intrinsic cellular mechanisms of persistent firing have been proposed, underlying cellular mechanisms are not yet fully understood. In vitro experiments have shown that individual neurons in the hippocampus and other working memory related areas support persistent firing through intrinsic cellular mechanisms that involve the transient receptor potential canonical (TRPC) channels. Recent behavioral studies demonstrating the involvement of TRPC channels on working memory make the hypothesis that TRPC driven persistent firing supports working memory a very attractive one. However, this view has been challenged by recent findings that persistent firing in vitro is unchanged in TRPC knock out (KO) mice. To assess the involvement of TRPC channels further, we tested novel and highly specific TRPC channel blockers in cholinergically induced persistent firing in mice CA1 pyramidal cells for the first time. -
Heteromeric TRP Channels in Lung Inflammation
cells Review Heteromeric TRP Channels in Lung Inflammation Meryam Zergane 1, Wolfgang M. Kuebler 1,2,3,4,5,* and Laura Michalick 1,2 1 Institute of Physiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; [email protected] (M.Z.); [email protected] (L.M.) 2 German Centre for Cardiovascular Research (DZHK), 10785 Berlin, Germany 3 German Center for Lung Research (DZL), 35392 Gießen, Germany 4 The Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada 5 Department of Surgery and Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada * Correspondence: [email protected] Abstract: Activation of Transient Receptor Potential (TRP) channels can disrupt endothelial bar- rier function, as their mediated Ca2+ influx activates the CaM (calmodulin)/MLCK (myosin light chain kinase)-signaling pathway, and thereby rearranges the cytoskeleton, increases endothelial permeability and thus can facilitate activation of inflammatory cells and formation of pulmonary edema. Interestingly, TRP channel subunits can build heterotetramers, whereas heteromeric TRPC1/4, TRPC3/6 and TRPV1/4 are expressed in the lung endothelium and could be targeted as a protec- tive strategy to reduce endothelial permeability in pulmonary inflammation. An update on TRP heteromers and their role in lung inflammation will be provided with this review. Keywords: heteromeric TRP assemblies; pulmonary inflammation; endothelial permeability; TRPC3/6; TRPV1/4; TRPC1/4 Citation: Zergane, M.; Kuebler, W.M.; Michalick, L. Heteromeric TRP Channels in Lung Inflammation. Cells 1. Introduction 2021, 10, 1654. https://doi.org Pulmonary microvascular endothelial cells are a key constituent of the blood air bar- /10.3390/cells10071654 rier that has to be extremely thin (<1 µm) to allow for rapid and efficient alveolo-capillary gas exchange. -
FKBP52 Regulates TRPC3-Dependent Ca<Sup>
© 2019. Published by The Company of Biologists Ltd | Journal of Cell Science (2019) 132, jcs231506. doi:10.1242/jcs.231506 RESEARCH ARTICLE FKBP52 regulates TRPC3-dependent Ca2+ signals and the hypertrophic growth of cardiomyocyte cultures Sandra Bandleon1, Patrick P. Strunz1, Simone Pickel2, Oleksandra Tiapko3, Antonella Cellini1, Erick Miranda-Laferte2 and Petra Eder-Negrin1,* ABSTRACT A single TRPC subunit is composed of six transmembrane The transient receptor potential (TRP; C-classical, TRPC) channel domains with a pore-forming loop connecting the transmembrane ‘ ’ TRPC3 allows a cation (Na+/Ca2+) influx that is favored by the domains 5 and 6, a preserved 25 amino acid sequence called a TRP domain and two cytosolic domains, an N-terminal ankyrin repeat stimulation of Gq protein-coupled receptors (GPCRs). An enhanced TRPC3 activity is related to adverse effects, including pathological domain and a C-terminal coiled-coil domain (Eder et al., 2007; Fan hypertrophy in chronic cardiac disease states. In the present study, et al., 2018). The cytosolic domains mediate ion channel formation we identified FK506-binding protein 52 (FKBP52, also known as and are implicated in ion channel regulation and plasma membrane FKBP4) as a novel interaction partner of TRPC3 in the heart. FKBP52 targeting (Eder et al., 2007). Among several protein interaction sites, was recovered from a cardiac cDNA library by a C-terminal TRPC3 the C-terminus of all TRPC subunits harbors a highly conserved fragment (amino acids 742–848) in a yeast two-hybrid screen. proline-rich sequence that corresponds to the binding domain in the Drosophila Downregulation of FKBP52 promoted a TRPC3-dependent photoreceptor channel TRPL for the FK506-binding hypertrophic response in neonatal rat cardiomyocytes (NRCs). -
Transient Receptor Potential Cation Channel, Subfamily C, Member 5 (TRPC5) Is a Cold-Transducer in the Peripheral Nervous System
Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system Katharina Zimmermanna,b,1,2, Jochen K. Lennerza,c,d,1,3, Alexander Heina,1,4, Andrea S. Linke, J. Stefan Kaczmareka,b, Markus Dellinga, Serdar Uysala, John D. Pfeiferc, Antonio Riccioa, and David E. Claphama,b,f,5 Departments of aCardiology, Manton Center for Orphan Disease, and bNeurobiology, Harvard Medical School, Boston, MA 02115; cDepartment of Pathology and Immunology, Washington University, St. Louis, MO, 63110; dDepartment of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 02116; eDepartment of Physiology and Pathophysiology, University Erlangen, 91054 Erlangen, Germany; and fHoward Hughes Medical Institute, Harvard Medical School, Children’s Hospital Boston, Boston, MA 02115 Contributed by David E. Clapham, September 20, 2011 (sent for review August 9, 2011) Detection and adaptation to cold temperature is crucial to survival. affected perforce by temperature, even if driven solely by con- Cold sensing in the innocuous range of cold (>10–15 °C) in the ventional NaV and KV channels—but high Q10 channels are likely mammalian peripheral nervous system is thought to rely primarily suspects in encoding temperature changes. Although TRPM8 on transient receptor potential (TRP) ion channels, most notably (a menthol receptor) is generally considered the primary cold – the menthol receptor, TRPM8. Here we report that TRP cation sensor for innocuous cold (11 13), and TRPA1 participates in channel, subfamily C member 5 (TRPC5), but not TRPC1/TRPC5 het- noxious cold sensing (9, 10) (14), many cold-sensitive neurons eromeric channels, are highly cold sensitive in the temperature lack TRPM8 as well as TRPA1 (15). -
1 Structural Basis of TRPC4 Regulation by Calmodulin And
bioRxiv preprint doi: https://doi.org/10.1101/2020.06.30.180778; this version posted July 1, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Structural basis of TRPC4 regulation by calmodulin and pharmacological agents 2 3 Deivanayagabarathy Vinayagam1, Dennis Quentin1, Oleg Sitsel1, Felipe Merino1,2, Markus 4 Stabrin1, Oliver Hofnagel1, Maolin Yu3, Mark W. Ledeboer3, Goran Malojcic3, Stefan 5 Raunser1 6 7 1Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 8 Dortmund, Germany 9 2Current address: Department of Protein Evolution, Max Planck Institute for Developmental 10 Biology, 72076 Tübingen, Germany 11 3Goldfinch Bio, 215 First St, Cambridge, MA 02142, USA 12 Correspondence: [email protected] 13 14 15 ABSTRACT 16 Canonical transient receptor potential channels (TRPC) are involved in receptor-operated 17 and/or store-operated Ca2+ signaling. Inhibition of TRPCs by small molecules was shown to be 18 promising in treating renal diseases. In cells, the channels are regulated by calmodulin. 19 Molecular details of both calmodulin and drug binding have remained elusive so far. Here we 20 report structures of TRPC4 in complex with a pyridazinone-based inhibitor and a pyridazinone- 21 based activator and calmodulin. The structures reveal that both activator and inhibitor bind to 22 the same cavity of the voltage-sensing-like domain and allow us to describe how structural 23 changes from the ligand binding site can be transmitted to the central ion-conducting pore of 24 TRPC4. -
Possible Involvement of Peripheral TRP Channels in the Hydrogen
Roa‑Coria et al. BMC Neurosci (2019) 20:1 https://doi.org/10.1186/s12868-018-0483-3 BMC Neuroscience RESEARCH ARTICLE Open Access Possible involvement of peripheral TRP channels in the hydrogen sulfde‑induced hyperalgesia in diabetic rats José Eduardo Roa‑Coria1, Jorge Baruch Pineda‑Farias2, Paulino Barragán‑Iglesias2, Geovanna Nallely Quiñonez‑Bastidas1, Ángel Zúñiga‑Romero1, Juan Carlos Huerta‑Cruz3, Juan Gerardo Reyes‑García1, Francisco Javier Flores‑Murrieta1,3, Vinicio Granados‑Soto2 and Héctor Isaac Rocha‑González1* Abstract Background: Peripheral diabetic neuropathy can be painful and its symptoms include hyperalgesia, allodynia and spontaneous pain. Hydrogen sulfde (H2S) is involved in diabetes-induced hyperalgesia and allodynia. However, the molecular target through which H2S induces hyperalgesia in diabetic animals is unclear. The aim of this study was to determine the possible involvement of transient receptor potential (TRP) channels in H2S-induced hyperalgesia in diabetic rats. Results: Streptozotocin (STZ) injection produced hyperglycemia in rats. Intraplantar injection of NaHS (an exog‑ enous donor of H2S, 3–100 µg/paw) induced hyperalgesia, in a time-dependent manner, in formalin-treated diabetic rats. NaHS-induced hyperalgesia was partially prevented by local intraplantar injection of capsazepine (0.3–3 µg/ paw), HC-030031 (100–316 µg/paw) and SKF-96365 (10–30 µg/paw) blockers, at 21 days post-STZ injection. At the doses used, these blockers did not modify formalin-induced nociception. Moreover, capsazepine (0.3–30 µg/paw), HC-030031 (100–1000 µg/paw) and SKF-96365 (10–100 µg/paw) reduced formalin-induced nociception in diabetic rats. Contralateral injection of the highest doses used did not modify formalin-induced finching behavior. -
The Structure of TRPC Ion Channels
Cell Calcium 80 (2019) 25–28 Contents lists available at ScienceDirect Cell Calcium journal homepage: www.elsevier.com/locate/ceca The structure of TRPC ion channels T ⁎ ⁎ Jian Lia,b, Xu Zhangc, Xiaojing Songc, Rui Liuc, Jin Zhangc, , Zongli Lid, a College of Pharmaceutical Sciences, Gannan Medical University, Ganzhou, Jiangxi, 341000, China b Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Ganan Medical University, Ganzhou, 341000, China c School of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi, 330031, China d Howard Hughes Medical Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA ARTICLE INFO ABSTRACT Keywords: Briefly review the recent structural work of transient receptor potential canonical (TRPC) ion channels by using TRPC electron cryo-microscopy (cryo-EM). The high resolution structures of TRPC3, TRPC4, TRPC5 and TRPC6 are Cryo-EM discussed. 1. Introduction cryo-EM method does not need protein to be crystallized and only use a few micron liter samples, and has thus greatly facilitate the structure Transient receptor potential canonical (TRPC) ion channels are determination of membrane proteins, especially the various ion chan- calcium-permeable, nonselective cation (Na+,K+,Ca2+) channels be- nels. Transient receptor potential canonical (TRPC) channels, important longing to the TRP superfamily [1–3]. They are expressed in many cell to the cell calcium homeostasis, are among them. Here we summarize types and tissues, including brain, placenta, adrenal gland, retina en- the recent development of the high resolution structure work of TRPC dothelia, testis, and kidney [4], and crucially involved in both the re- ion channels. -
TRPC6-Dependent Ca2+ Signaling Mediates Airway Inflammation In
Chen et al. Cell Death and Disease (2020) 11:170 https://doi.org/10.1038/s41419-020-2360-0 Cell Death & Disease ARTICLE Open Access TRPC6-dependent Ca2+ signaling mediates airway inflammation in response to oxidative stress via ERK pathway Qingzi Chen 1,YuboZhou1, Lifen Zhou1, Zhaodi Fu1, Chuntao Yang1, Lei Zhao1,ShuniLi1, Yan Chen1,YousenWu1, Zhenwei Ling2,YufengWang1, Jianrong Huang3 and Jianhua Li1 Abstract Ozone (O3) plays an extremely important role in airway inflammation by generating reactive oxygen species (ROS) including hydrogen peroxide, then promoting redox actions and causing oxidative stress. Evidences indicate that TRPC6 (canonical transient receptor potential channel 6) is a redox-regulated Ca2+ permeable nonselective cation channel, but its role in the setting of oxidative stress-related airway inflammation remains unknown. Here, we found that both TRPC6−/− mice and mice pretreated with SAR7334, a potent TRPC6 inhibitor, were protected from O3-induced airway inflammatory responses. In vitro, both knockdown of TRPC6 expression with shRNA and TRPC6 blockage markedly attenuated the release of cytokines IL-6 and IL-8 induced by O3 or H2O2 in 16HBE cells (human bronchial epithelial cell line). Treatment with O3 or H2O2 enhanced TRPC6 protein expression in vivo and vitro. We also 2+ 2+ observed that TRPC6-dependent increase of intracellular Ca concentration ([Ca ]i) was triggered by H2O2, which consisted of the release from intracellular calcium store and the influx of extracellular Ca2+ and could be further strengthened by 6-h O3 exposure in both 16HBE cells and HBEpiCs (primary human bronchial epithelial cells). fi fl 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; Moreover, we con rmed that the activation of MAPK signals (ERK1/2, p38, JNK) was required for the in ammatory response induced by O3 or H2O2 while only the phosphorylation of ERK pathway was diminished in the TRPC6- knockdown situation.