title: Phospholipase Cgamma1 controls surface expression of TRPC3 through an intermolecular PH domain.
abstract: Many ion channels are regulated by lipids, but prominent motifs for lipid binding have not been identified in most ion channels. Recently, we reported that phospholipase Cgamma1 (PLC-gamma1) binds to and regulates TRPC3 channels, components of agonist-induced Ca2+ entry into cells. This interaction requires a domain in PLC-gamma1 that includes a partial pleckstrin homology (PH) domain-a consensus lipid-binding and protein-binding sequence. 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-gamma1 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.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Damian B
authors.initials: DB
authors.lastname: van Rossum
authors.forename: Randen L
authors.initials: RL
authors.lastname: Patterson
authors.forename: Sumit
authors.initials: S
authors.lastname: Sharma
authors.forename: Roxanne K
authors.initials: RK
authors.lastname: Barrow
authors.forename: Michael
authors.initials: M
authors.lastname: Kornberg
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gill
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D020134:Catalytic Domain; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D019295:Computational Biology; D030562:Databases, Protein; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D006801:Humans; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D051966:Phospholipase C gamma; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D015398:Signal Transduction; D050052:TRPC Cation Channels; D020798:Two-Hybrid System Techniques; D010738:Type C Phospholipases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D007473:Ion Channels; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium