Dual action of the G alpha(q)-PLC beta-PI(4,5) P-2 pathway on TRPC1/4 and TRPC1/5 heterotetramers

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 G alpha(q)-PLCO pathway is self-limited and dynamically mediated by G alpha(q) and PI(4,5)P-2. We provide evidence indicating that Gag protein directly interacts with eitherTRPC4 or TRPC5 of the heterotetrameric channels to permit activation. Simultaneously, G alpha(q)-coupled PLCO activation leads to the breakdown of PI(4,5)P-2, which inhibits activity of TRPC1/4 and 1/5 channels.