Polycystins under Pressure

Polycystin-1 and -2 Dosage Regulates Pressure Sensing

Autosomal-dominant polycystic kidney disease, the most frequent monogenic cause of kidney failure, is induced by mutations in the PKD1 or PKD2 genes, encoding polycystins TRPP1 and TRPP2, respectively. Polycystins are proposed to form a flow-sensitive ion channel complex in the primary cilium of both epithelial and endothelial cells. However, how polycystins contribute to cellular mechanosensit...

A latent capacity of the C. elegans polycystins to disrupt sensory transduction is repressed by the single-pass ciliary membrane protein CWP-5.

Autosomal dominant polycystic kidney disease (ADPKD) results from loss-of-function mutations in PKD1 or PKD2. The products of these genes, the polycystins PC-1 and PC-2, form a transmembrane channel that is necessary for flow sensing by renal cilia. In C. elegans, the polycystin orthologs LOV-1 and PKD-2 function in sensory neurons that mediate male mating behavior. Here, we report that the nov...

Mechanoprotection by polycystins against apoptosis is mediated through the opening of stretch-activated K(2P) channels.

How renal epithelial cells respond to increased pressure and the link with kidney disease states remain poorly understood. Pkd1 knockout or expression of a PC2 pathogenic mutant, mimicking the autosomal dominant polycystic kidney disease, dramatically enhances mechanical stress-induced tubular apoptotic cell death. We show the presence of a stretch-activated K(+) channel dependent on the TREK-2...

The KLP-6 Kinesin Is Required for Male Mating Behaviors and Polycystin Localization in Caenorhabditis elegans

BACKGROUND Male mating behavior of the nematode Caenorhabditis elegans offers an intriguing model to study the genetics of sensory behavior, cilia function, and autosomal dominant polycystic kidney disease (ADPKD). The C. elegans polycystins LOV-1 and PKD-2 act in male-specific sensory cilia required for response and vulva-location mating behaviors. RESULTS Here, we identify and characterize ...

Polycystins and mechanotransduction in bone