Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC1 , TRPP , TRPP1 , TRPV , TRPV4

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

Authors: Juan Du, Xin Ma, Bing Shen, Yu Huang, Lutz Birnbaumer, Xiaoqiang Yao

Journal, date & volume: FASEB J., 2014 Nov , 28, 4677-85

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25114176

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.