TRP channels in renal disease. Lessons from Polycystin-2 (TRPP2)

Abstract

The TRP (transient receptor potential) channel superfamily comprises at least 27 related transmembrane proteins categorized into subfamilies, including TRPC, TRPV, TRPM, TRPA1, TRPML, and the polycystins (TRPP). Concerning renal function, there is a consensus that TRP channels play an essential role in calcium (Ca2+) homeostasis. TRPV channels are related to osmosensation, sodium and fluid balance, and fibrosis. TRPCs are implicated in blood pressure regulation. TRPMs are associated with renal ischemia-reperfusion damage and Ca2+ homeostasis. TRPA1 channels are expressed in sensory nerves in the kidney and nociception. TRPPs are related to polycystic kidney diseases. Specifically, PKD2 gene encoding polycystin-2 (TRPP2, PC2) mutations are associated with autosomal dominant and recessive polycystic kidney disease (ADPKD and ARKD, respectively). As a TRP protein superfamily member, PC2 is a Ca2+-permeable nonselective cation channel that plays a central role in Ca2+ signaling. PC2 is located in various cellular regions with distinct functions and interactions with specific channel partners that influence its activities. These functions include receptor-operated nonselective cation channel activity in the plasma membrane, intracellular Ca2+ release channel activity in the endoplasmic reticulum (ER), and mechanosensitive channel activity in the primary cilium of renal epithelial cells.