TY - JOUR
T1 - Gating of the polycystin ion channel signaling complex in neurons and kidney cells.
AU - Delmas, Patrick
AU - Nauli, Surya M.
AU - Li, Xiaogang
AU - Coste, Bertrand
AU - Osorio, Nancy
AU - Crest, Marcel
AU - Brown, David A.
AU - Zhou, Jing
PY - 2004/4
Y1 - 2004/4
N2 - 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.
AB - 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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U2 - 10.1096/fj.03-0319fje
DO - 10.1096/fj.03-0319fje
M3 - Article
C2 - 14766803
AN - SCOPUS:3042739908
SN - 0892-6638
VL - 18
SP - 740
EP - 742
JO - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
JF - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
IS - 6
ER -