Title

Gating of the Polycystin Ion Channel Signaling Complex in Neurons and Kidney Cells

Document Type

Article

Publication Date

4-2004

Abstract

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 G(i/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.

Comments

This article was originally published in FASEB Journal, volume 18, issue 6, in April 2004. DOI: 10.1096/fj.03-0319fje

Copyright

Federation of American Societies for Experimental Biology