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

Membrane phosphoinositides control a variety of cellular processes through the recruitment and/or regulation of cytosolic proteins^1-4. 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 1γ (PtdInsPKIγ) is a phosphatidylinositol-4-phosphate 5-kinase that is expressed at high levels in brain, and is concentrated at synapses^5,6. Here we show that the predominant brain splice variant of PtdInsPKIγ (PtdInsPKIγ-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 plaques⁷, is also present at synapses. PtdInsPKIγ-90 is expressed in non- neuronal cells, albeit at much lower levels than in neurons, and is concentrated at focal adhesion plaques, where phosphatidyl-inositol-4,5-bisphosphate has an important regulatory role. Overexpression of PtdInsPKIγ-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.