Abstract:

Transient receptor potential canonical (TRPC) proteins form Ca2+-permeable nonselective cation channels that are activated downstream from receptors that signal through phospholipase C (PLC). Among the seven mammalian TRPC isoforms, TRPC4 and TRPC5 are unique in that they are also responsive to Gi/o proteins, which allows them to respond to coincident activation of Gq/11-PLC and Gi/o signaling pathways. In addition, TRPC4 channels are subject to dual regulation by phosphatidylinositol 4,5-bisphosphate (PIP2), the substrate of PLC, and cytosolic Ca2+, the product of TRPC4 activation. These ensure that the channel activity is finely tuned to meet the demand of the cellular function. Such a tightly controlled activity should have special attributes to cellular functions that require precise spatiotemporal regulation. However, despite its involvement in various physiological processes, a unifying cellular function or molecular target(s) that can fully explain the mechanistic underpinnings of TRPC-dependent physiological activities has not been identified. Moreover, the role of the Ca2+ signal generated by TRPCs in these physiological activities remains to be fully elucidated. This presentation will discuss the current thinking about TRPC channel regulation and function, using TRPC4 as the main example.