Polycystin-1: function as a mechanosensor.
Polycystin-1 (PC1), encoded by the Pkd1 gene, is a large transmembrane protein whose mutation is involved in autosomal dominant polycystic kidney disease. When expressed, PC1 activates a G-protein signaling pathway that subsequently modulates Ca(2+) channels. PC1 is highly expressed in developing tissue and via its C-terminus tail forms a complex with polycystin-2; this complex, found to be located at the primary cilia, seems to act as a mechanosensor that could affect proliferation, differentiation and apoptosis of cells. Also, loss of polycystins correlates with disruption of flow-dependent and steady-state intracellular Ca(2+) signaling. Despite the lack of clarity on the role of the polycystins as mechanosensor molecules, a new interest in this PCs/primary cilium complex is providing continuously new insights. In this review, some of the known features of PC1 such as structure, function, signaling pathways involved and its role as a possible therapeutic target are being discussed.
Dalagiorgou
Georgia
G
Department of Biological Chemistry, University of Athens Medical School, Athens, Greece.
Basdra
Efthimia K
EK
Papavassiliou
Athanasios G
AG
D020013:Calcium Signaling; D002454:Cell Differentiation; D049109:Cell Proliferation; D002923:Cilia / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008465:Mechanoreceptors / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D009154:Mutation / Q000235:genetics; D007690:Polycystic Kidney Diseases / Q000235:genetics*; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D050396:TRPP Cation Channels