New aspects of the contribution of ER to SOCE regulation TRPC proteins as a link between plasma membrane ion transport and intracellular Ca²⁺ stores

Transient receptor potential canonical (TRPC) proteins were identified as molecular candidates of receptor- and/or store-operated channels because of their close homology to the Drosophila TRP and TRPL. Functional studies have revealed that TRPC channels play an integrated part of phospholipase C-transduced cell signaling, mediating Ca²⁺, as well as Na⁺, influx into cells. As a consequence, the TRPC channels have diverse functional roles in difference cell types, including metabotropic receptor-evoked membrane depolarization and intracellular Ca²⁺ concentration regulation. Depending on the cellular environment and the protein partners present in the channel complex, the TRPC channels display different biophysical properties and mechanisms of regulation. Despite the controversy on whether or not TRPC channels are store-operated, evidence exists for physical and functional interactions between plasma membrane-localized TRPC channels and proteins involved in sensing and regulating the intracellular Ca²⁺ store contents, such as inositol trisphosphate receptors, junctate, STIM, and Homer. The interplay among these proteins will likely define the functional significance of TRPC channel activation in different cellular contexts and under different modes of stimulations.