| pubmed-article:14766803 | pubmed:abstractText | Mutations in either polycystin-2 (PC2) or polycystin-1 (PC1) proteins cause severe, potentially lethal, kidney disorders and multiple extrarenal (including brain) disease phenotypes. PC2, a member of the transient receptor potential channel superfamily, and PC1, an orphan membrane receptor of largely unknown function, are thought to be part of a common signaling pathway. Here, we show that in rat sympathetic neurons and kidney cells, coassembly of full-length PC1 with PC2 forms a plasmalemmal ion channel signaling complex in which PC1 stimulation simultaneously activates PC2 ion channels and Gi/o-proteins. PC2 activation occurs through a structural rearrangement of PC1, independent of G-protein activation. Thus, PC1 acts as a prototypical membrane receptor that concordantly regulates PC2 channels and G-proteins, a bimodal mechanism that may account for the multifunctional roles of polycystin proteins in fundamental cellular processes of various cell types. | lld:pubmed |
