TRPP2 ion channels: The roles in various subcellular locations

Abstract

TRPP2 (PC2, PKD2 or Polycytin-2), encoded by PKD2 gene, belongs to the nonselective cation channel TRP family. Recently, the three-dimensional structure of TRPP2 was constructed. TRPP2 mainly functions in three subcellular compartments: endoplasmic reticulum, plasma membrane and primary cilia. TRPP2 can act as a calcium-activated intracellular calcium release channel on the endoplasmic reticulum. TRPP2 also interacts with other Ca²⁺ release channels to regulate calcium release, like IP3R and RyR2. TRPP2 acts as an ion channel regulated by epidermal growth factor through activation of downstream factors in the plasma membrane. TRPP2 binding to TRPC1 in the plasma membrane or endoplasmic reticulum is associated with mechanosensitivity. In cilium, TRPP2 was found to combine with PKD1 and TRPV4 to form a complex related to mechanosensitivity. Because TRPP2 is involved in regulating intracellular ion concentration, TRPP2 mutations often lead to autosomal dominant polycystic kidney disease, which may also be associated with cardiovascular disease. In this paper, we review the molecular structure of TRPP2, the subcellular localization of TRPP2, the related functions and mechanisms of TRPP2 at different sites, and the diseases related to TRPP2.

Keywords: ADPKD; Ca(2+) ion channel; TRP channel; TRPP2.