Recruitment and regulation of phosphatidylinositol phosphate kinase type 1γ by the FERM domain of talin
Recruitment and regulation of phosphatidylinositol phosphate kinase type 1γ by the FERM domain of talin
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DOI：
10.1038/nature01147
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发表时间：
2002-11-07
期刊：
影响因子：
64.8
通讯作者：
De Camilli, P
中科院分区：
文献类型：
--
作者：
Di Paolo, G;Pellegrini, L;De Camilli, P
膜磷酸肌醇通过募集和/或调节胞质蛋白来控制多种细胞过程（1 - 4）。确保磷酸肌醇信号传导具有空间特异性的一种机制是将介导其代谢的酶靶向特定的亚细胞位点。1型磷脂酰肌醇磷酸激酶γ（PtdInsPKIγ）是一种磷脂酰肌醇 - 4 - 磷酸5 - 激酶，在大脑中高水平表达，并集中在突触处（5,6）。在此我们表明，PtdInsPKIγ的主要大脑剪接变体（PtdInsPKIγ - 90）通过一个短的羧基末端肽与踝蛋白的FERM结构域结合，并通过这种相互作用被强烈激活。踝蛋白是粘着斑的主要成分（7），也存在于突触中。PtdInsPKIγ - 90在非神经元细胞中表达，尽管其水平比在神经元中低得多，并且集中在粘着斑处，在那里磷脂酰肌醇 - 4,5 - 二磷酸具有重要的调节作用。PtdInsPKIγ - 90的过表达，或者其羧基末端结构域的表达，可能通过局部破坏正常的磷酸肌醇平衡而破坏粘着斑。这些发现确定了一种在细胞粘附中具有调节作用的相互作用，并提示了构成突触连接的分子相互作用与细胞粘附的一般机制之间的新的相似性。
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 1gamma (PtdInsPKIgamma) 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 PtdInsPKIg (PtdInsPKIgamma-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 7,is also present at synapses. PtdInsPKIgamma-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 PtdInsPKIgamma-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.