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FASEB J. 2014 Nov;28(11):4677-85. doi: 10.1096/fj.14-251652. Epub 2014 Aug 11.

TRPV4, TRPC1, and TRPP2 assemble to form a flow-sensitive heteromeric channel.

Author information

1
School of Biomedical Sciences and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China; Department of Physiology, Anhui Medical University, He Fei, China; and.
2
School of Biomedical Sciences and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China;
3
National Institute of Environmental Health Sciences, U.S. National Institutes of Health, Research Triangle Park, North Carolina, USA.
4
School of Biomedical Sciences and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China; yao2068@cuhk.edu.hk.

Abstract

Transient receptor potential (TRP) channels, a superfamily of ion channels, can be divided into 7 subfamilies, including TRPV, TRPC, TRPP, and 4 others. Functional TRP channels are tetrameric complexes consisting of 4 pore-forming subunits. The purpose of this study was to explore the heteromerization of TRP subunits crossing different TRP subfamilies. Two-step coimmunoprecipitation (co-IP) and fluorescence resonance energy transfer (FRET) were used to determine the interaction of the different TRP subunits. Patch-clamp and cytosolic Ca(2+) measurements were used to determine the functional role of the ion channels in flow conditions. The analysis demonstrated the formation of a heteromeric TRPV4-C1-P2 complex in primary cultured rat mesenteric artery endothelial cells (MAECs) and HEK293 cells that were cotransfected with TRPV4, TRPC1, and TRPP2. In functional experiments, pore-dead mutants for each of these 3 TRP isoforms nearly abolished the flow-induced cation currents and Ca(2+) increase, suggesting that all 3 TRPs contribute to the ion permeation pore of the channels. We identified the first heteromeric TRP channels composed of subunits from 3 different TRP subfamilies. Functionally, this heteromeric TRPV4-C1-P2 channel mediates the flow-induced Ca(2+) increase in native vascular endothelial cells.

KEYWORDS:

Ca2+; endothelial cells; mesenteric artery; shear stress

PMID:
25114176
PMCID:
PMC4200325
DOI:
10.1096/fj.14-251652
[Indexed for MEDLINE]
Free PMC Article

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