TRPM4b Channel Suppresses Store-Operated Ca2+ Entry by a Novel Protein-Protein Interaction With the TRPC3 Channel

Biochem Biophys Res Commun. 2008 Apr 11;368(3):677-83. doi: 10.1016/j.bbrc.2008.01.153. Epub 2008 Feb 8.

Abstract

We identified human TRPC3 protein by yeast two-hybrid screening of a human brain cDNA library with human TRPM4b as a bait. Immunoprecipitation and confocal microscopic analyses confirmed the protein-protein interaction between TRPM4b and TRPC3, and these two TRPs were found to be highly colocalized at the plasma membrane of HEK293T cells. Overexpression of TRPM4b suppressed TRPC3-mediated whole cell currents by more than 90% compared to those in TRPC3-expressed HEK293T cells. Furthermore, HEK293T cells stably overexpressing red fluorescent protein (RFP)-TRPM4b exhibited an almost complete abolition of UTP-induced store-operated Ca(2+) entry, which is known to take place via endogenous TRPC channels in HEK293T cells. This study is believed to provide the first clear evidence that TRPM4b interacts physically with TRPC3, a member of a different TRP subfamily, and regulates negatively the channel activity, in turn suppressing store-operated Ca(2+) entry through the TRPC3 channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Cell Line
  • Humans
  • Ion Channel Gating / physiology*
  • Kidney / metabolism*
  • Protein Binding
  • Protein Interaction Mapping
  • TRPC Cation Channels / metabolism*
  • TRPM Cation Channels / metabolism*

Substances

  • TRPC Cation Channels
  • TRPC3 cation channel
  • TRPM Cation Channels
  • TRPM4 protein, human
  • Calcium