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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.
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pubmed:affiliation |
Intégration des Informations Sensorielles (UMR 6150), CNRS, Faculté de Médecine, IFR Jean Roche, Bd. P. Dramard, 13916 Marseille, Cedex 20, France. delmas.p@jean-roche.univ-mrs.fr
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