title: TRPV4, TRPC1, and TRPP2 assemble to form a flow-sensitive heteromeric channel.
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.
authors.affiliation: 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.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: School of Biomedical Sciences and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China;
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.affiliation: School of Biomedical Sciences and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China;
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: National Institute of Environmental Health Sciences, U.S. National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.affiliation: School of Biomedical Sciences and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China; yao2068@cuhk.edu.hk.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yao
mesh_terms: D000818:Animals; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008638:Mesenteric Arteries / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D050052:TRPC Cation Channels / Q000378:metabolism*; D050396:TRPP Cation Channels / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000378:metabolism
chemical_list: D050052:TRPC Cation Channels; D050396:TRPP Cation Channels; D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; D050051:Transient Receptor Potential Channels; C486577:Trpv4 protein, rat; C096351:transient receptor potential cation channel, subfamily C, member 1
keywords: Ca2+; endothelial cells; mesenteric artery; shear stress
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