Structure of the Mouse TRPC4 Ion Channel
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Genetic Analysis of the Shaker Gene Complex of Drosophila Melanogaster
Copyright 0 1990 by the Genetics Society of America Genetic Analysisof the Shaker Gene Complexof Drosophila melanogaster A. Ferriis,* S. LLamazares,* J. L. de la Pornpa,* M. A. Tanouye? and0. Pongs* *Institute Cajal, CSIC, 28006 Madrid, Spain, +California Instituteof Technology, Pasadena, California 91 125, and 'Ruhr Universitat,Bochum, Federal Republic of Germany Manuscript received May 10, 1989 Accepted for publication March 3, 1990 ABSTRACT The Shaker complex (ShC) spans over 350 kb in the 16F region of the X chromosome. It can be dissected by means of aneuploids into three main sections: the maternal effect (ME), the viable (V) and the haplolethal (HL) regions. The mutational analysis of ShC shows a high density of antimorphic mutations among 12 lethal complementation groupsin addition to 14 viable alleles. The complex is the structural locus of a family of potassium channels as well as a number of functions relevant to the biology of the nervous system. The constituents of ShC seem to be linked by functional relationships in view of the similarity of the phenotypes, antimorphic nature of their mutations and the behavior in transheterozygotes. We discuss the relationship between the genetic organization of ShC and the functional coupling of potassium currents with the other functions encodedin the complex. HAKER was the first behavioral mutant detected do not appear tohave the capability of generating, by S in Drosophila melanogaster (CATSCH1944). It was themselves, gated ionic channels. named after another mutantwith a similar phenotype K+ currents are known to be themost diverse class isolated earlier in Drosophila funebris (LUERS 1936). of ionic currents in terms of kinetics, pharmacology The original phenotype was described as the trem- and sensitivity (HILLE 1984; RUDY 1988).Also, these bling of appendagesin the anesthetized fly. -
The Role of Transient Receptor Potential Cation Channels in Ca2þ Signaling
Downloaded from http://cshperspectives.cshlp.org/ on October 7, 2021 - Published by Cold Spring Harbor Laboratory Press The Role of Transient Receptor Potential Cation Channels in Ca2þ Signaling Maarten Gees, Barbara Colsoul, and Bernd Nilius KU Leuven, Department of Molecular Cell Biology, Laboratory Ion Channel Research, Campus Gasthuisberg, Herestraat 49, bus 802, Leuven, Belgium Correspondence: [email protected] The 28 mammalian members of the super-family of transient receptor potential (TRP) channels are cation channels, mostly permeable to both monovalent and divalent cations, and can be subdivided into six main subfamilies: the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and the TRPA (ankyrin) groups. TRP channels are widely expressed in a large number of different tissues and cell types, and their biological roles appear to be equally diverse. In general, considered as poly- modal cell sensors, they play a much more diverse role than anticipated. Functionally, TRP channels, when activated, cause cell depolarization, which may trigger a plethora of voltage-dependent ion channels. Upon stimulation, Ca2þ permeable TRP channels 2þ 2þ 2þ generate changes in the intracellular Ca concentration, [Ca ]i,byCa entry via the plasma membrane. However, more and more evidence is arising that TRP channels are also located in intracellular organelles and serve as intracellular Ca2þ release channels. This review focuses on three major tasks of TRP channels: (1) the function of TRP channels as Ca2þ entry channels; (2) the electrogenic actions of TRPs; and (3) TRPs as Ca2þ release channels in intracellular organelles. ransient receptor potential (TRP) channels choanoflagellates, yeast, and fungi are primary Tconstitute a large and functionally versatile chemo-, thermo-, or mechanosensors (Cai 2008; family of cation-conducting channel proteins, Wheeler and Brownlee 2008; Chang et al. -
The Structural Basis for an On–Off Switch Controlling Gβγ-Mediated Inhibition of TRPM3 Channels
The structural basis for an on–off switch controlling Gβγ-mediated inhibition of TRPM3 channels Marc Behrendta,b,1,2, Fabian Grussc,1,3, Raissa Enzerotha,b, Sandeep Demblaa,b, Siyuan Zhaod, Pierre-Antoine Crassousd, Florian Mohra, Mieke Nysc, Nikolaos Lourose, Rodrigo Gallardoe,4, Valentina Zorzinif,5, Doris Wagnera, Anastassios Economou (Αναστάσιoς Οικoνόμoυ)f, Frederic Rousseaue, Joost Schymkowitze, Stephan E. Philippg, Tibor Rohacsd, Chris Ulensc,6, and Johannes Oberwinklera,b,6 aInstitut für Physiologie und Pathophysiologie, Philipps-Universität Marburg, 35037 Marburg, Germany;bCenter for Mind, Brain and Behavior (CMBB), Philipps-Universität Marburg and Justus-Liebig-Universität Giessen, 35032 Marburg, Germany; cLaboratory of Structural Neurobiology, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium; dDepartment of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ 07103; eSwitch Laboratory, VIB Center for Brain and Disease Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium; fLaboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium; and gExperimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany Edited by László Csanády, Semmelweis University, Budapest, Hungary, and accepted by Editorial Board Member David E. Clapham August 27, 2020 (received for review February 13, 2020) TRPM3 channels play important roles in the detection of noxious also subject to inhibition by activated μORsorotherGPCRs(6, heat and in inflammatory thermal hyperalgesia. The activity of 24–28), a process that has been shown to take place in peripheral these ion channels in somatosensory neurons is tightly regulated by endings of nociceptive neurons since locally applied μOR or μ βγ -opioid receptors through the signaling of G proteins, thereby GABA receptor agonists inhibit TRPM3-dependent pain (24–26). -
Transient Receptor Potential Channel Promiscuity Frustrates Constellation
the sole sensor responsible for noxious cold responses in M+A+ LETTER neurons (1). However, TRPA1 is also activated by cooling and underlies at least part of the noxious cold responsiveness of Transient receptor potential channel AITC-sensitive neurons (3). Third, the authors used nicardipine 2+ promiscuity frustrates to selectively inhibit CaV1-type voltage-gated Ca channels (1). However, several dihydropyridines, including nicardipine, also constellation pharmacology act as TRPA1 agonists (4). These considerations led us to propose an alternative Sensory neurons from the trigeminal and dorsal root ganglia molecular interpretation of the difference between M+A− (DRG) have nerve endings in the skin and mucosa, where they and M+A+ neurons, which is in much better agreement with detect environmental stimuli and convey this information to published work. In accord with the authors, we conclude that the central nervous system. Several members of the transient M+A− neurons express TRPM8 but lack expression of receptor potential (TRP) superfamily of ion channels act as TRPA1. In contrast to the authors, we propose that M+A+ prime molecular sensors for thermal and chemical stimuli in neurons express TRPA1 as the prime cold and menthol these sensory neurons. However, it is incompletely understood sensor (2, 3). This interpretation is consistent with published how TRP channel expression and modulation affect the stimulus observations that menthol responses in M+A− but not in sensitivities of distinct neuronal subtypes. M+A+ neurons are inhibited by TRPM8 antagonists (5) In a recent article, Teichert et al. (1) described a “constellation and that TRPA1-mediated responses to cold in neurons are pharmacology approach” to identify and characterize subtypes characterized by a higher (colder) threshold (3). -
Chapter Four – TRPA1 Channels: Chemical and Temperature Sensitivity
CHAPTER FOUR TRPA1 Channels: Chemical and Temperature Sensitivity Willem J. Laursen1,2, Sviatoslav N. Bagriantsev1,* and Elena O. Gracheva1,2,* 1Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA 2Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT, USA *Corresponding author: E-mail: [email protected], [email protected] Contents 1. Introduction 90 2. Activation and Regulation of TRPA1 by Chemical Compounds 91 2.1 Chemical activation of TRPA1 by covalent modification 91 2.2 Noncovalent activation of TRPA1 97 2.3 Receptor-operated activation of TRPA1 99 3. Temperature Sensitivity of TRPA1 101 3.1 TRPA1 in mammals 101 3.2 TRPA1 in insects and worms 103 3.3 TRPA1 in fish, birds, reptiles, and amphibians 103 3.4 TRPA1: Molecular mechanism of temperature sensitivity 104 Acknowledgments 107 References 107 Abstract Transient receptor potential ankyrin 1 (TRPA1) is a polymodal excitatory ion channel found in sensory neurons of different organisms, ranging from worms to humans. Since its discovery as an uncharacterized transmembrane protein in human fibroblasts, TRPA1 has become one of the most intensively studied ion channels. Its function has been linked to regulation of heat and cold perception, mechanosensitivity, hearing, inflam- mation, pain, circadian rhythms, chemoreception, and other processes. Some of these proposed functions remain controversial, while others have gathered considerable experimental support. A truly polymodal ion channel, TRPA1 is activated by various stimuli, including electrophilic chemicals, oxygen, temperature, and mechanical force, yet the molecular mechanism of TRPA1 gating remains obscure. In this review, we discuss recent advances in the understanding of TRPA1 physiology, pharmacology, and molecular function. -
The TRPP2-Dependent Channel of Renal Primary Cilia Also Requires TRPM3
The TRPP2-dependent channel of renal primary cilia also requires TRPM3 Steven J. Kleene1, Brian J. Siroky2, Julio A. Landero-Figueroa3, Bradley P. Dixon4, Nolan W. Pachciarz2, Lu Lu2, and Nancy K. Kleene1 1Department of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, Ohio; 2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; 3Department of Chemistry, University of Cincinnati, Cincinnati, Ohio; 4Renal Section, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado IntroductIon Primary cilia of renal epithelial cells express several members of the transient receptor potential (TRP) class of cation-conducting channel, including TRPC1, TRPM3, TRPM4, TRPP2, and TRPV4. Some cases of autosomal dominant polycystic kidney disease (ADPKD) are caused by defects in TRPP2 (also called polycystin-2, PC2, or PKD2). A large-conductance, TRPP2- dependent channel in renal cilia has been well described, but it is not known whether this channel includes any other protein subunits. Methods To study this question, we investigated the pharmacology of the TRPP2-dependent channel through electrical recordings from the cilia of mIMCD-3 cells, a murine cell line of renal epithelial origin, results The pharmacology was found to match that of TRPM3 channels. The ciliary TRPP2-dependent channel is known to be activated by depolarization and/or increasing cytoplasmic Ca2+. This activation was greatly enhanced by external pregnenolone sulfate, an agonist of TRPM3 channels. Pregnenolone sulfate did not change the current-voltage relation of the channel. CIM0216, another TRPM3 agonist, modestly increased the activity of the ciliary channels. The channels were effectively blocked by isosakuranetin, a specific inhibitor of TRPM3 channels. -
Trpc, Trpv and Vascular Disease | Encyclopedia
TRPC, TRPV and Vascular Disease Subjects: Biochemistry Submitted by: Tarik Smani Hajami Definition Ion channels play an important role in vascular function and pathology. In this review we gave an overview of recent findings and discussed the role of TRPC and TRPV channels as major regulators of cellular remodeling and consequent vascular disorders. Here, we focused on their implication in 4 relevant vascular diseases: systemic and pulmonary artery hypertension, atherosclerosis and restenosis. Transient receptor potentials (TRPs) are non-selective cation channels that are widely expressed in vascular beds. They contribute to the Ca2+ influx evoked by a wide spectrum of chemical and physical stimuli, both in endothelial and vascular smooth muscle cells. Within the superfamily of TRP channels, different isoforms of TRPC (canonical) and TRPV (vanilloid) have emerged as important regulators of vascular tone and blood flow pressure. Additionally, several lines of evidence derived from animal models, and even from human subjects, highlighted the role of TRPC and TRPV in vascular remodeling and disease. Dysregulation in the function and/or expression of TRPC and TRPV isoforms likely regulates vascular smooth muscle cells switching from a contractile to a synthetic phenotype. This process contributes to the development and progression of vascular disorders, such as systemic and pulmonary arterial hypertension, atherosclerosis and restenosis. 1. Introduction Blood vessels are composed essentially of two interacting cell types: endothelial cells (ECs) from the tunica intima lining of the vessel wall and vascular smooth muscle cells (VSMCs) from tunica media of the vascular tube. Blood vessels are a complex network, and they differ according to the tissue to which they belong, having diverse cell expressions, structures and functions [1][2][3]. -
Expression Profiling of Ion Channel Genes Predicts Clinical Outcome in Breast Cancer
UCSF UC San Francisco Previously Published Works Title Expression profiling of ion channel genes predicts clinical outcome in breast cancer Permalink https://escholarship.org/uc/item/1zq9j4nw Journal Molecular Cancer, 12(1) ISSN 1476-4598 Authors Ko, Jae-Hong Ko, Eun A Gu, Wanjun et al. Publication Date 2013-09-22 DOI http://dx.doi.org/10.1186/1476-4598-12-106 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Ko et al. Molecular Cancer 2013, 12:106 http://www.molecular-cancer.com/content/12/1/106 RESEARCH Open Access Expression profiling of ion channel genes predicts clinical outcome in breast cancer Jae-Hong Ko1, Eun A Ko2, Wanjun Gu3, Inja Lim1, Hyoweon Bang1* and Tong Zhou4,5* Abstract Background: Ion channels play a critical role in a wide variety of biological processes, including the development of human cancer. However, the overall impact of ion channels on tumorigenicity in breast cancer remains controversial. Methods: We conduct microarray meta-analysis on 280 ion channel genes. We identify candidate ion channels that are implicated in breast cancer based on gene expression profiling. We test the relationship between the expression of ion channel genes and p53 mutation status, ER status, and histological tumor grade in the discovery cohort. A molecular signature consisting of ion channel genes (IC30) is identified by Spearman’s rank correlation test conducted between tumor grade and gene expression. A risk scoring system is developed based on IC30. We test the prognostic power of IC30 in the discovery and seven validation cohorts by both Cox proportional hazard regression and log-rank test. -
Transient Receptor Potential (TRP) Channels in Haematological Malignancies: an Update
biomolecules Review Transient Receptor Potential (TRP) Channels in Haematological Malignancies: An Update Federica Maggi 1,2 , Maria Beatrice Morelli 2 , Massimo Nabissi 2 , Oliviero Marinelli 2 , Laura Zeppa 2, Cristina Aguzzi 2, Giorgio Santoni 2 and Consuelo Amantini 3,* 1 Department of Molecular Medicine, Sapienza University, 00185 Rome, Italy; [email protected] 2 Immunopathology Laboratory, School of Pharmacy, University of Camerino, 62032 Camerino, Italy; [email protected] (M.B.M.); [email protected] (M.N.); [email protected] (O.M.); [email protected] (L.Z.); [email protected] (C.A.); [email protected] (G.S.) 3 Immunopathology Laboratory, School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy * Correspondence: [email protected]; Tel.: +30-0737403312 Abstract: Transient receptor potential (TRP) channels are improving their importance in differ- ent cancers, becoming suitable as promising candidates for precision medicine. Their important contribution in calcium trafficking inside and outside cells is coming to light from many papers published so far. Encouraging results on the correlation between TRP and overall survival (OS) and progression-free survival (PFS) in cancer patients are available, and there are as many promising data from in vitro studies. For what concerns haematological malignancy, the role of TRPs is still not elucidated, and data regarding TRP channel expression have demonstrated great variability throughout blood cancer so far. Thus, the aim of this review is to highlight the most recent findings Citation: Maggi, F.; Morelli, M.B.; on TRP channels in leukaemia and lymphoma, demonstrating their important contribution in the Nabissi, M.; Marinelli, O.; Zeppa, L.; perspective of personalised therapies. -
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. -
Molecular Characterization of TRPA Subfamily Genes and Function in Temperature Preference in Tuta Absoluta (Meyrick) (Lepidoptera: Gelechiidae)
International Journal of Molecular Sciences Article Molecular Characterization of TRPA Subfamily Genes and Function in Temperature Preference in Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) Xiao-Di Wang 1, Ze-Kai Lin 1 , Shun-Xia Ji 1, Si-Yan Bi 1, Wan-Xue Liu 1, Gui-Fen Zhang 1, Fang-Hao Wan 1,2 and Zhi-Chuang Lü 1,* 1 State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China; [email protected] (X.-D.W.); [email protected] (Z.-K.L.); [email protected] (S.-X.J.); [email protected] (S.-Y.B.); [email protected] (W.-X.L.); [email protected] (G.-F.Z.); [email protected] (F.-H.W.) 2 Agricultural Genome Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China * Correspondence: [email protected]; Tel.: +86-10-8210-9572 Abstract: To reveal the mechanism of temperature preference in Tuta absoluta, one of the top 20 plant pests in the world, we cloned and identified TaTRPA1, TaPain, and TaPyx genes by RACE and bioinformatic analysis, and clarified their expression profiles during different development stages using real-time PCR, and revealed their function in preference temperature by RNAi. The full-length cDNA of TaPain was 3136 bp, with a 2865-bp open reading frame encoding a 259.89-kDa Citation: Wang, X.-D.; Lin, Z.-K.; Ji, protein; and the partial length cDNA of TaPyx was 2326-bp, with a 2025-bp open reading frame S.-X.; Bi, S.-Y.; Liu, W.-X.; Zhang, G.-F.; encoding a 193.16-kDa protein. -
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.