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Store depletion induces Gαq-mediated PLCβ1 activity to stimulate TRPC1 channels in vascular smooth muscle cells.

Shi, J; Miralles, F; Birnbaumer, L; Large, WA; Albert, AP (2015) Store depletion induces Gαq-mediated PLCβ1 activity to stimulate TRPC1 channels in vascular smooth muscle cells. The FASEB Journal, 30 (2). pp. 702-715. ISSN 0892-6638 https://doi.org/10.1096/fj.15-280271
SGUL Authors: Albert, Anthony Paul Miralles Arenas, Francisco Shi, Jian

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Abstract

Depletion of sarcoplasmic reticulum (SR) Ca(2+) stores activates store-operated channels (SOCs) composed of canonical transient receptor potential (TRPC) 1 proteins in vascular smooth muscle cells (VSMCs), which contribute to important cellular functions. We have previously shown that PKC is obligatory for activation of TRPC1 SOCs in VSMCs, and the present study investigates if the classic phosphoinositol signaling pathway involving Gαq-mediated PLC activity is responsible for driving PKC-dependent channel gating. The G-protein inhibitor GDP-β-S, anti-Gαq antibodies, the PLC inhibitor U73122, and the PKC inhibitor GF109203X all inhibited activation of TRPC1 SOCs, and U73122 and GF109203X also reduced store-operated PKC-dependent phosphorylation of TRPC1 proteins. Three distinct SR Ca(2+) store-depleting agents, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, cyclopiazonic acid, and N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamineed, induced translocations of the fluorescent biosensor GFP-PLCδ1-PH from the cell membrane to the cytosol, which were inhibited by U73122. Knockdown of PLCβ1 with small hairpin RNA reduced both store-operated PLC activity and stimulation of TRPC1 SOCs. Immunoprecipitation studies and proximity ligation assays revealed that store depletion induced interactions between TRPC1 and Gαq, and TRPC1 and PLCβ1. We propose a novel activation mechanism for TRPC1 SOCs in VSMCs, in which store depletion induces formation of TRPC1-Gαq-PLCβ1 complexes that lead to PKC stimulation and channel gating.-Shi, J., Miralles, F., Birnbaumer, L., Large, W. A., Albert, A. P. Store depletion induces Gαq-mediated PLCβ1 activity to stimulate TRPC1 channels in vascular smooth muscle cells.

Item Type: Article
Additional Information: © The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Ca2+ signaling, PLC activity, electrophysiology, phosphoinositol signaling, Biochemistry & Molecular Biology, 0601 Biochemistry And Cell Biology, 0606 Physiology, 1116 Medical Physiology
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Vascular (INCCVA)
Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: The FASEB Journal
ISSN: 0892-6638
Language: eng
Dates:
DateEvent
14 October 2015Published
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
BB/J007226/1Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/M018350/1Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
PubMed ID: 26467792
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107684
Publisher's version: https://doi.org/10.1096/fj.15-280271

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