1. Departments of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
2. Pharmacology and Molecular Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
3. Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
4. Department of Biology, The Pennsylvania State University, State College, Pennsylvania 16802, USA
5. Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
6. These authors contributed equally to this work

Correspondence to: Solomon H. Snyder^1,2,3 Correspondence and requests for materials should be addressed to S.H.S. (Email: ssnyder@jhmi.edu).

Abstract

Many ion channels are regulated by lipids^{1, 2, 3}, but prominent motifs for lipid binding have not been identified in most ion channels. Recently, we reported that phospholipase C1 (PLC-1) binds to and regulates TRPC3 channels⁴, components of agonist-induced Ca²⁺ entry into cells. This interaction requires a domain in PLC-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-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.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.