1. Howard Hughes Medical Institute and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
2. These authors contributed equally to this work
3. Present addresses: University of Pennsylvania, Wharton School of Business, Philadelphia, Pennsylvania 19104, USA (L.P.); Laboratory of Cellular Neurobiology, Department of Life Science K-JIST, 1 Oryoung-dong, Puk-gu, Kwang-ju 500-712, Republic of Korea (S.C.).

Correspondence to: Pietro De Camilli¹ Correspondence and requests for materials should be addressed to P.D.C. (e-mail: Email: pietro.decamilli@yale.edu).

Abstract

Membrane phosphoinositides control a variety of cellular processes through the recruitment and/or regulation of cytosolic proteins^{1, 2, 3, 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 1 (PtdInsPKI) 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 PtdInsPKI (PtdInsPKI-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. PtdInsPKI-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-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.