Phospholipase C[gamma]1 controls surface expression of TRPC3 through an intermolecular PH domain.
van Rossum, Damian B. 1*; Patterson, Randen L. 4*; Sharma, Sumit 1; Barrow, Roxanne K. 1; Kornberg, Michael 1; Gill, Donald L. 5; Snyder, Solomon H. 1,2,3
[Letter] Nature. 434(7029):99-104, March 3, 2005.

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Many ion channels are regulated by lipids 1-3, but prominent motifs for lipid binding have not been identified in most ion channels. Recently, we reported that phospholipase C[gamma]1 (PLC-[gamma]1) binds to and regulates TRPC3 channels 4, components of agonist-induced Ca2 entry into cells. This interaction requires a domain in PLC-[gamma]1 that includes a partial pleckstrin homology (PH) domain-a consensus lipid-binding and protein-binding sequence 5,6. We have developed a gestalt algorithm to detect hitherto 'invisible' PH and PH-like domains, and now report that the partial PH domain of PLC-[gamma]1 interacts with a complementary partial PH-like domain in TRPC3 to elicit lipid binding and cell-surface expression of TRPC3. Our findings imply a far greater abundance of PH domains than previously appreciated, and suggest that intermolecular PH-like domains represent a widespread signalling mode.

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