High-Resolution Structures of TRPV Channels: Unveiling a Functionally
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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. -
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]. -
Disease-Associated Mutations in TRPM3 Render the Channel Overactive Via Two Distinct Mechanisms
bioRxiv preprint doi: https://doi.org/10.1101/2020.04.20.052167; this version posted April 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Disease-associated mutations in TRPM3 render the channel overactive via two distinct mechanisms Siyuan Zhao, Yevgen Yudin, Tibor Rohacs Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers University, Newark, NJ ABSTRACT Transient Receptor Potential Melastatin 3 (TRPM3) is a Ca2+ permeable non-selective cation channel activated by heat and chemical agonists such as pregnenolone sulfate and CIM0216. TRPM3 mutations in humans were recently reported to be associated with intellectual disability and epilepsy; the functional effects of those mutations however were not reported. Here we show that both disease-associated mutations of TRPM3 render the channel overactive, but likely via different mechanisms. The Val to Met substitution in the S4-S5 loop induced a larger increase in basal activity and agonist sensitivity at room temperature than the Pro to Gln substitution in the extracellular segment of S6. In contrast, heat activation was increased more by the S6 mutant than by the S4-S5 segment mutant. Both mutants were inhibited by the TRPM3 antagonist primidone, suggesting a potential therapeutic intervention to treat this disease. INTRODUCTION Transient Receptor Potential Melastatin 3 (TRPM3) is a Ca2+ permeable, non-selective cation channel activated by heat (Vriens et al., 2011) and chemical activators such as the neurosteroid pregnenolone sulfate (PregS) (Wagner et al., 2008) and the synthetic compound CIM0216 (Held et al., 2015). -
TRPM8 Channels and Dry Eye
UC Berkeley UC Berkeley Previously Published Works Title TRPM8 Channels and Dry Eye. Permalink https://escholarship.org/uc/item/2gz2d8s3 Journal Pharmaceuticals (Basel, Switzerland), 11(4) ISSN 1424-8247 Authors Yang, Jee Myung Wei, Edward T Kim, Seong Jin et al. Publication Date 2018-11-15 DOI 10.3390/ph11040125 Peer reviewed eScholarship.org Powered by the California Digital Library University of California pharmaceuticals Review TRPM8 Channels and Dry Eye Jee Myung Yang 1,2 , Edward T. Wei 3, Seong Jin Kim 4 and Kyung Chul Yoon 1,* 1 Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwangju 61469, Korea; [email protected] 2 Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea 3 School of Public Health, University of California, Berkeley, CA 94720, USA; [email protected] 4 Department of Dermatology, Chonnam National University Medical School and Hospital, Gwangju 61469, Korea; [email protected] * Correspondence: [email protected] Received: 17 September 2018; Accepted: 12 November 2018; Published: 15 November 2018 Abstract: Transient receptor potential (TRP) channels transduce signals of chemical irritation and temperature change from the ocular surface to the brain. Dry eye disease (DED) is a multifactorial disorder wherein the eyes react to trivial stimuli with abnormal sensations, such as dryness, blurring, presence of foreign body, discomfort, irritation, and pain. There is increasing evidence of TRP channel dysfunction (i.e., TRPV1 and TRPM8) in DED pathophysiology. Here, we review some of this literature and discuss one strategy on how to manage DED using a TRPM8 agonist. -
New Natural Agonists of the Transient Receptor Potential Ankyrin 1 (TRPA1
www.nature.com/scientificreports OPEN New natural agonists of the transient receptor potential Ankyrin 1 (TRPA1) channel Coline Legrand, Jenny Meylan Merlini, Carole de Senarclens‑Bezençon & Stéphanie Michlig* The transient receptor potential (TRP) channels family are cationic channels involved in various physiological processes as pain, infammation, metabolism, swallowing function, gut motility, thermoregulation or adipogenesis. In the oral cavity, TRP channels are involved in chemesthesis, the sensory chemical transduction of spicy ingredients. Among them, TRPA1 is activated by natural molecules producing pungent, tingling or irritating sensations during their consumption. TRPA1 can be activated by diferent chemicals found in plants or spices such as the electrophiles isothiocyanates, thiosulfnates or unsaturated aldehydes. TRPA1 has been as well associated to various physiological mechanisms like gut motility, infammation or pain. Cinnamaldehyde, its well known potent agonist from cinnamon, is reported to impact metabolism and exert anti-obesity and anti-hyperglycemic efects. Recently, a structurally similar molecule to cinnamaldehyde, cuminaldehyde was shown to possess anti-obesity and anti-hyperglycemic efect as well. We hypothesized that both cinnamaldehyde and cuminaldehyde might exert this metabolic efects through TRPA1 activation and evaluated the impact of cuminaldehyde on TRPA1. The results presented here show that cuminaldehyde activates TRPA1 as well. Additionally, a new natural agonist of TRPA1, tiglic aldehyde, was identifed -
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-/- -
TRPV4: a Physio and Pathophysiologically Significant Ion Channel
International Journal of Molecular Sciences Review TRPV4: A Physio and Pathophysiologically Significant Ion Channel Tamara Rosenbaum 1,* , Miguel Benítez-Angeles 1, Raúl Sánchez-Hernández 1, Sara Luz Morales-Lázaro 1, Marcia Hiriart 1 , Luis Eduardo Morales-Buenrostro 2 and Francisco Torres-Quiroz 3 1 Departamento de Neurociencia Cognitiva, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; [email protected] (M.B.-A.); [email protected] (R.S.-H.); [email protected] (S.L.M.-L.); [email protected] (M.H.) 2 Departamento de Nefrología y Metabolismo Mineral, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico; [email protected] 3 Departamento de Bioquímica y Biología Estructural, División Investigación Básica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; [email protected] * Correspondence: [email protected]; Tel.: +52-555-622-56-24; Fax: +52-555-622-56-07 Received: 3 May 2020; Accepted: 24 May 2020; Published: 28 May 2020 Abstract: Transient Receptor Potential (TRP) channels are a family of ion channels whose members are distributed among all kinds of animals, from invertebrates to vertebrates. The importance of these molecules is exemplified by the variety of physiological roles they play. Perhaps, the most extensively studied member of this family is the TRPV1 ion channel; nonetheless, the activity of TRPV4 has been associated to several physio and pathophysiological processes, and its dysfunction can lead to severe consequences. Several lines of evidence derived from animal models and even clinical trials in humans highlight TRPV4 as a therapeutic target and as a protein that will receive even more attention in the near future, as will be reviewed here. -
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. -
Ca Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart
Journal of Cardiovascular Development and Disease Review Ca2+ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases Jianlin Feng 1, Maria K. Armillei 1, Albert S. Yu 1, Bruce T. Liang 1, Loren W. Runnels 2,* and Lixia Yue 1,* 1 Calhoun Cardiology Center, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA; [email protected] (J.F.); [email protected] (M.K.A.); [email protected] (A.S.Y.); [email protected] (B.T.L.) 2 Department of Pharmacology, Rutgers, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA * Correspondence: [email protected] (L.W.R.); [email protected] (L.Y.) Received: 11 August 2019; Accepted: 18 September 2019; Published: 23 September 2019 Abstract: Cardiac fibrosis is the excessive deposition of extracellular matrix proteins by cardiac fibroblasts and myofibroblasts, and is a hallmark feature of most heart diseases, including arrhythmia, hypertrophy, and heart failure. This maladaptive process occurs in response to a variety of stimuli, including myocardial injury, inflammation, and mechanical overload. There are multiple signaling pathways and various cell types that influence the fibrogenesis cascade. Fibroblasts and myofibroblasts are central effectors. Although it is clear that Ca2+ signaling plays a vital role in this pathological process, what contributes to Ca2+ signaling in fibroblasts and myofibroblasts is still not wholly understood, chiefly because of the large and diverse number of receptors, transporters, and ion channels that influence intracellular Ca2+ signaling. Intracellular Ca2+ signals are generated by Ca2+ release from intracellular Ca2+ stores and by Ca2+ entry through a multitude of Ca2+-permeable ion channels in the plasma membrane. -
Macromolecular Assembly of Polycystin-2 Intracytosolic C-Terminal Domain
Macromolecular assembly of polycystin-2 intracytosolic C-terminal domain Frederico M. Ferreiraa,b,1, Leandro C. Oliveirac, Gregory G. Germinod, José N. Onuchicc,1, and Luiz F. Onuchica,1 aDivision of Nephrology, University of São Paulo School of Medicine, 01246-903, São Paulo, Brazil; bLaboratory of Immunology, Heart Institute, University of São Paulo School of Medicine, 05403-900, São Paulo, Brazil; cCenter for Theoretical Biological Physics, University of California at San Diego, La Jolla, CA 92093; dNational Institute of Diabetes, Digestive, and Kidney Diseases, Bethesda, MD 20892-2560 Contributed by José N. Onuchic, April 28, 2011 (sent for review March 20, 2011) Mutations in PKD2 are responsible for approximately 15% of the In spite of the aforementioned information and insights, the autosomal dominant polycystic kidney disease cases. This gene macromolecular assembly of PC2t homooligomer continued to encodes polycystin-2, a calcium-permeable cation channel whose be an open question. In the current work, we present the most C-terminal intracytosolic tail (PC2t) plays an important role in its comprehensive set of analyses yet performed and that show interaction with a number of different proteins. In the present PC2t forms a homotetrameric oligomer. We have proposed a study, we have comprehensively evaluated the macromolecular PC2 C-terminal domain delimitation and submitted it to a range assembly of PC2t homooligomer using a series of biophysical of biochemical and biophysical evaluations, including chemical and biochemical analyses. Our studies, based on a new delimitation cross-linking, dynamic light scattering (DLS), circular dichroism of PC2t, have revealed that it is capable of assembling as a homo- (CD) and small angle X-ray scattering (SAXS) analyses. -
(TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6) Gene and Protein Expression in Patients with Ulcerative Colitis
Hindawi Journal of Immunology Research Volume 2020, Article ID 2906845, 11 pages https://doi.org/10.1155/2020/2906845 Research Article TRPV Subfamily (TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6) Gene and Protein Expression in Patients with Ulcerative Colitis Joel J. Toledo Mauriño,1,2 Gabriela Fonseca-Camarillo ,1 Janette Furuzawa-Carballeda ,3 Rafael Barreto-Zuñiga,4 Braulio Martínez Benítez ,5 Julio Granados ,6 and Jesus K. Yamamoto-Furusho 1 1Inflammatory Bowel Disease Clinic. Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico 2MD/PhD Program (PECEM), Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Ciudad Universitaria 3000, C.P. 04360 Coyoacán, México City, Mexico 3Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico 4Department of Endoscopy, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico 5Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico 6Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico Correspondence should be addressed to Jesus K. Yamamoto-Furusho; [email protected] Received 25 October 2019; Revised 4 March 2020; Accepted 11 April 2020; Published 8 May 2020 Academic Editor: Francesca Santilli Copyright © 2020 Joel J. Toledo Mauriño et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction. TRPVs are a group of receptors with a channel activity predominantly permeable to Ca2+. This subfamily is involved in the development of gastrointestinal diseases such as ulcerative colitis (UC). -
Microarray Analysis Reveals the Inhibition of Intestinal Expression Of
www.nature.com/scientificreports OPEN Microarray analysis reveals the inhibition of intestinal expression of nutrient transporters in piglets infected with porcine epidemic diarrhea virus Junmei Zhang1,3, Di Zhao1,3, Dan Yi1,3, Mengjun Wu1, Hongbo Chen1, Tao Wu1, Jia Zhou1, Peng Li1, Yongqing Hou1* & Guoyao Wu2 Porcine epidemic diarrhea virus (PEDV) infection can induce intestinal dysfunction, resulting in severe diarrhea and even death, but the mode of action underlying these viral efects remains unclear. This study determined the efects of PEDV infection on intestinal absorption and the expression of genes for nutrient transporters via biochemical tests and microarray analysis. Sixteen 7-day-old healthy piglets fed a milk replacer were randomly allocated to one of two groups. After 5-day adaption, piglets (n = 8/ group) were orally administrated with either sterile saline or PEDV (the strain from Yunnan province) 4.5 at 10 TCID50 (50% tissue culture infectious dose) per pig. All pigs were orally infused D-xylose (0.1 g/ kg BW) on day 5 post PEDV or saline administration. One hour later, jugular vein blood samples as well as intestinal samples were collected for further analysis. In comparison with the control group, PEDV infection increased diarrhea incidence, blood diamine oxidase activity, and iFABP level, while reducing growth and plasma D-xylose concentration in piglets. Moreover, PEDV infection altered plasma and jejunal amino acid profles, and decreased the expression of aquaporins and amino acid transporters (L-type amino acid