Hosted by: Chang-Jun Liu

Mutations in TRPP2 and PKD1 account for almost all clinically identified cases of autosomal dominant polycystic kidney disease (ADPKD), one of the most common human genetic diseases. TRPP2 and PKD1 form a receptor-ion channel complex on primary cilia and couple extracellular stimuli to cellular responses in renal cells. We found that this complex contains three TRPP2 subunits and one PKD1 subunit, and this 3:1 stoichiometry is determined by a coiled-coil domain on the C-terminus of TRPP2. Our data also suggested that PKD proteins may be involved in channel pore-forming, in addition to signal reception. Furthermore, by generating a gain-of-function TRPP2 mutant, we investigated the functional property of TRPP2, which was largely unknown due to the lack of the knowledge on the activation mechanism of this ion channel.