Phospholipase Cgamma1 controls surface expression of TRPC3 through an intermolecular PH domain.
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.
van Rossum
Damian B
DB
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Patterson
Randen L
RL
Sharma
Sumit
S
Barrow
Roxanne K
RK
Kornberg
Michael
M
Gill
Donald L
DL
Snyder
Solomon H
SH
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*
D007473:Ion Channels; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium