Dual action of the Gαq-PLCβ-PI(4,5)P2 pathway on TRPC1/4 and TRPC1/5 heterotetramers

Sci Rep. 2018 Aug 14;8(1):12117. doi: 10.1038/s41598-018-30625-0.

Abstract

The transient receptor potential canonical (TRPC) 1 channel is widely distributed in mammalian cells and is involved in many physiological processes. TRPC1 is primarily considered a regulatory subunit that forms heterotetrameric channels with either TRPC4 or TRPC5 subunits. Here, we suggest that the regulation of TRPC1/4 and TRPC1/5 heterotetrameric channels by the Gαq-PLCβ pathway is self-limited and dynamically mediated by Gαq and PI(4,5)P2. We provide evidence indicating that Gαq protein directly interacts with either TRPC4 or TRPC5 of the heterotetrameric channels to permit activation. Simultaneously, Gαq-coupled PLCβ activation leads to the breakdown of PI(4,5)P2, which inhibits activity of TRPC1/4 and 1/5 channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • HEK293 Cells
  • Humans
  • Patch-Clamp Techniques
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Phospholipase C beta / metabolism
  • Protein Multimerization / physiology*
  • Signal Transduction / physiology*
  • TRPC Cation Channels / metabolism*

Substances

  • Phosphatidylinositol 4,5-Diphosphate
  • TRPC Cation Channels
  • TRPC4 ion channel
  • TRPC5 protein, human
  • transient receptor potential cation channel, subfamily C, member 1
  • Phospholipase C beta
  • GTP-Binding Protein alpha Subunits, Gq-G11