The functions of TRPP2 in the vascular system

Abstract

TRPP2 (polycystin-2, PC2 or PKD2), encoded by the PKD2 gene, is a non-selective cation channel with a large single channel conductance and high Ca(2+) permeability. In cell membrane, TRPP2, along with polycystin-1, TRPV4 and TRPC1, functions as a mechanotransduction channel. In the endoplasmic reticulum, TRPP2 modulates intracellular Ca(2+) release associated with IP3 receptors and the ryanodine receptors. Noteworthily, TRPP2 is widely expressed in vascular endothelial and smooth muscle cells of all major vascular beds, and contributes to the regulation of vessel function. The mutation of the PKD2 gene is a major cause of autosomal dominant polycystic kidney disease (ADPKD), which is not only a common genetic disease of the kidney but also a systemic disorder associated with abnormalities in the vasculature; cardiovascular complications are the leading cause of mortality and morbidity in ADPKD patients. This review provides an overview of the current knowledge regarding the TRPP2 protein and its possible role in cardiovascular function and related diseases.

Figure 1

The structural features of a TRPP2 channel. A single TRPP2 subunit comprises six transmembrane segments (S1–S6) with a cation-permeable pore between S5 and S6. In the cytoplasmic C-terminus, there are EF-hands, a coiled-coil domain, and an acidic amino acid cluster. Four such units assemble into an ion channel.