TRPC1: a core component of store-operated calcium channels.
The TRPC (transient receptor potential canonical) proteins are activated in response to agonist-stimulated PIP(2) (phosphatidylinositol 4,5-bisphosphate) hydrolysis and have been suggested as candidate components of the elusive SOC (store-operated calcium channel). TRPC1 is currently the strongest candidate component of SOC. Endogenous TRPC1 has been shown to contribute to SOCE (store-operated calcium entry) in several different cell types. However, the mechanisms involved in the regulation of TRPC1 and its exact physiological function have yet to be established. Studies from our laboratory and several others have demonstrated that TRPC1 is assembled in a signalling complex with key calcium signalling proteins in functionally specific plasma membrane microdomains. Furthermore, critical interactions between TRPC1 monomers as well as interactions between TRPC1 and other proteins determine the surface expression and function of TRPC1-containing channels. Recent studies have revealed novel regulators of TRPC1-containing SOCs and have demonstrated a common molecular basis for the regulation of CRAC (calcium-release-activated calcium) and SOC channels. In the present paper, we will revisit the role of TRPC1 in SOCE and discuss how studies with TRPC1 provide an experimental basis for validating the mechanism of SOCE.
Ambudkar
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Building 10, Room 1N-113, Secretory Physiology Section, GTTB (Gene Therapy and Therapeutics Branch), NIDCR (National Institute of Dental And Craniofacial Research), NIH (National Institutes of Health), Bethesda, MD 20892, USA. indu.ambudkar@nih.gov
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry*; D020013:Calcium Signaling; D005786:Gene Expression Regulation; D006801:Humans; D007473:Ion Channels / Q000737:chemistry; D021962:Membrane Microdomains / Q000737:chemistry; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D050052:TRPC Cation Channels / Q000737:chemistry* / Q000502:physiology*
D015220:Calcium Channels; D007473:Ion Channels; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D002118:Calcium