title: Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin.
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.
authors.affiliation: Howard Hughes Medical Institute and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Di Paolo
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pellegrini
authors.forename: Kresimir
authors.initials: K
authors.lastname: Letinic
authors.forename: Gianluca
authors.initials: G
authors.lastname: Cestra
authors.forename: Roberto
authors.initials: R
authors.lastname: Zoncu
authors.forename: Sergei
authors.initials: S
authors.lastname: Voronov
authors.forename: Sunghoe
authors.initials: S
authors.lastname: Chang
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
mesh_terms: D016475:3T3 Cells; D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000378:metabolism*; D004789:Enzyme Activation; D022001:Focal Adhesions; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013569:Synapses / Q000201:enzymology / Q000378:metabolism; D016608:Talin
chemical_list: D003598:Cytoskeletal Proteins; D007527:Isoenzymes; D019269:Phosphatidylinositol 4,5-Diphosphate; C436513:TLN2 protein, human; D016608:Talin; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase