Ca2+ signaling microdomains:: platforms for the assembly and regulation of TRPC channels

The transient receptor potential canonical family (TRPC1-TRPC7) of ion channel proteins, which are activated in response to agonist-stimulated phosphatidylinositol (4,5)-bisphosphate [Ptdlns(4,5)P-2] hydrolysis, are proposed components of the elusive store-operated Ca2+ (SOC) channel. TRPC channels display distinct properties and interact to form homomeric or heteromeric channels that differ in their function and regulation. Although the exact function of TRPC channels and how they are regulated has not been established, increasing data suggest that they are localized and regulated within Ca2+ signaling microdomains. TRPC channels contribute to store-operated and store-independent Ca2+ entry mechanisms, both of which are activated by agonist-stimulated Ptdlns(4,5)P-2 hydrolysis. Elucidation of how cells achieve specificity and precise temporal and spatial coordination of channel activation is crucial for understanding the molecular basis of agonist-mediated stimulation of Ca2+ entry and identifying downstream physiological functions. This review will address the assembly and localization of TRPC channels and how these processes impact their function.