A tale of two tails: ciliary mechanotransduction in ADPKD.
Autosomal dominant polycystic kidney disease (ADPKD) is a common lethal genetic disorder, characterized by the progressive development of fluid-filled cysts in the kidney, pancreas and liver, and anomalies of the cardiovascular system. Mutations in PKD1 and PKD2, which encode the transmembrane proteins polycystin-1 (PC1) and polycystin-2 (PC2) respectively, account for almost all cases of ADPKD. However, the mechanisms by which abnormalities in PKD1 and PKD2 lead to aberrant kidney development remain unknown. Recent progress in the understanding of ADPKD has focused on primary cilia, which act as sensory transducers in renal epithelial cells. New evidence shows that a mechanosensitive signal, cilia bending, activates the PC1-PC2 channel complex. When working properly, this functional complex elicits a transient Ca(2+) influx, which is coupled to the release of Ca(2+) from intracellular stores.
Cantiello
Horacio F
HF
Renal Unit, Massachusetts General Hospital East, 149 13th Street, Charlestown, MA 02129, USA. cantiello@helix.mgh.harvard.edu
D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002923:Cilia / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D050396:TRPP Cation Channels
D002135:Calcium-Binding Proteins; D011506:Proteins; D050396:TRPP Cation Channels