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

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.
Mesh Terms:
3T3 Cells, Alternative Splicing, Animals, Brain, Cell Adhesion, Cytoskeletal Proteins, Enzyme Activation, Focal Adhesions, Humans, Isoenzymes, Mice, Phosphatidylinositol 4,5-Diphosphate, Phosphotransferases (Alcohol Group Acceptor), Protein Binding, Protein Structure, Tertiary, Synapses, Talin
Nature
Date: Nov. 07, 2002
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