Organization and function of TRPC channelosomes.
TRPC proteins constitute a family of conserved Ca2+-permeable cation channels which are activated in response to agonist-stimulated PIP2 hydrolysis. These channels were initially proposed to be components of the store-operated calcium entry channel (SOC). Subsequent studies have provided substantial evidence that some TRPCs contribute to SOC activity. TRPC proteins have also been shown to form agonist-stimulated calcium entry channels that are not store-operated but are likely regulated by PIP2 or diacylglycerol. Further, and consistent with the presently available data, selective homomeric or heteromeric interactions between TRPC monomers generate distinct agonist-stimulated cation permeable channels. We suggest that interaction between TRPC monomers, as well as the association of these channels with accessory proteins, determines their mode of regulation as well as their cellular localization and function. Currently identified accessory proteins include key Ca2+ signaling proteins as well as proteins involved in vesicle trafficking, cytoskeletal interactions, and scaffolding. Studies reported until now demonstrate that TRPC proteins are segregated into specific Ca2+ signaling complexes which can generate spatially and temporally controlled [Ca2+]i signals. Thus, the functional organization of TRPC channelosomes dictates not only their regulation by extracellular stimuli but also serves as a platform to coordinate specific downstream cellular functions that are regulated as a consequence of Ca2+ entry. This review will focus on the accessory proteins of TRPC channels and discuss the functional implications of TRPC channelosomes and their assembly in microdomains.
Ambudkar
Indu S
IS
Secretory Physiology Section, Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. indu.ambudkar@nih.gov
Ong
Hwei Ling
HL
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D004075:Diglycerides / Q000502:physiology; D006801:Humans; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000502:physiology; D050052:TRPC Cation Channels / Q000502:physiology*
D004075:Diglycerides; D019269:Phosphatidylinositol 4,5-Diphosphate; D050052:TRPC Cation Channels