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

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


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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Endothelial Cells / metabolism
  • Humans
  • Mesenteric Arteries / metabolism
  • Rats, Sprague-Dawley
  • TRPC Cation Channels / metabolism*
  • TRPP Cation Channels / metabolism*
  • TRPV Cation Channels / metabolism*
  • Transient Receptor Potential Channels / metabolism


  • TRPC Cation Channels
  • TRPP Cation Channels
  • TRPV Cation Channels
  • TRPV4 protein, human
  • Transient Receptor Potential Channels
  • Trpv4 protein, rat
  • transient receptor potential cation channel, subfamily C, member 1