Phospholipase Cgamma1 controls surface expression of TRPC3 through an intermolecular PH domain

Nature. 2005 Mar 3;434(7029):99-104. doi: 10.1038/nature03340.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calcium / metabolism
  • Catalytic Domain
  • Cell Line
  • Cell Membrane / metabolism*
  • Computational Biology
  • Databases, Protein
  • Gene Expression Regulation*
  • Genetic Complementation Test
  • Humans
  • Ion Channels / chemistry*
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Lipid Metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Phospholipase C gamma
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats
  • Signal Transduction
  • TRPC Cation Channels
  • Two-Hybrid System Techniques
  • Type C Phospholipases / chemistry*
  • Type C Phospholipases / genetics
  • Type C Phospholipases / metabolism*

Substances

  • Ion Channels
  • TRPC Cation Channels
  • TRPC3 cation channel
  • Type C Phospholipases
  • Phospholipase C gamma
  • Calcium