Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin

Nature. 2002 Nov 7;420(6911):85-9. doi: 10.1038/nature01147.

Abstract

Membrane phosphoinositides control a variety of cellular processes through the recruitment and/or regulation of cytosolic proteins. One mechanism ensuring spatial specificity in phosphoinositide signalling is the targeting of enzymes that mediate their metabolism to specific subcellular sites. Phosphatidylinositol phosphate kinase type 1 gamma (PtdInsPKI gamma) is a phosphatidylinositol-4-phosphate 5-kinase that is expressed at high levels in brain, and is concentrated at synapses. Here we show that the predominant brain splice variant of PtdInsPKI gamma (PtdInsPKI gamma-90) binds, by means of a short carboxy-terminal peptide, to the FERM domain of talin, and is strongly activated by this interaction. Talin, a principal component of focal adhesion plaques, is also present at synapses. PtdInsPKI gamma-90 is expressed in non-neuronal cells, albeit at much lower levels than in neurons, and is concentrated at focal adhesion plaques, where phosphatidylinositol-4,5-bisphosphate has an important regulatory role. Overexpression of PtdInsPKI gamma-90, or expression of its C-terminal domain, disrupts focal adhesion plaques, probably by local disruption of normal phosphoinositide balance. These findings define an interaction that has a regulatory role in cell adhesion and suggest new similarities between molecular interactions underlying synaptic junctions and general mechanisms of cell adhesion.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Alternative Splicing
  • Animals
  • Brain / enzymology
  • Brain / metabolism
  • Cell Adhesion
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / metabolism*
  • Enzyme Activation
  • Focal Adhesions*
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism
  • Mice
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / chemistry
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Synapses / enzymology
  • Synapses / metabolism
  • Talin

Substances

  • Cytoskeletal Proteins
  • Isoenzymes
  • Phosphatidylinositol 4,5-Diphosphate
  • TLN2 protein, human
  • Talin
  • Phosphotransferases (Alcohol Group Acceptor)
  • 1-phosphatidylinositol-4-phosphate 5-kinase