Recruitment and regulation of phosphatidylinositol phosphate kinase type 1γ by the FERM domain of talin
| Autor: | Sunghoe Chang, Pietro De Camilli, Gianluca Cestra, Jun Guo, Gilbert Di Paolo, Lorenzo Pellegrini, Roberto Zoncu, Sergei Voronov, Markus R. Wenk, Kresimir Letinic |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate Talin PTK2 Biology Focal adhesion Mice chemistry.chemical_compound Cell Adhesion Animals Humans Phosphatidylinositol Cell adhesion Focal Adhesions Multidisciplinary FERM domain Kinase Brain 3T3 Cells Talin binding Protein Structure Tertiary Cell biology Enzyme Activation Isoenzymes Alternative Splicing Cytoskeletal Proteins Phosphotransferases (Alcohol Group Acceptor) chemistry Synapses Phosphatidylinositol phosphate kinases Protein Binding |
| Zdroj: | Nature. 420:85-89 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature01147 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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