Gilmore A P, Burridge K
Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill, 27599, USA.
Nature. 1996 Jun 6;381(6582):531-5. doi: 10.1038/381531a0.
Vinculin, a prominent cytoskeletal protein at cell-substrate adhesions (focal adhesions) and cell-cell adhesions (adherens junctions), interacts with other cytoskeletal proteins, including talin and actin. An intramolecular interaction between the head and tail domains of vinculin masks the binding sites for both proteins. The exposure of cryptic binding sites may be important for promoting focal adhesion assembly. Several agents that induce the formation of focal adhesions act through the GTP-binding protein Rho, which elevates phosphatidylinositol-4,5-bisphosphate (PtdInsP2) levels by activating phosphatidyl-inositol-4-phosphate-5-OH kinase (PtdIns-5-OH kinase). PtdInsP2 regulates several actin-binding proteins, including profilin, gelsolin and alpha-actinin, and interacts with vinculin. Here we report that PtdInsP2 dissociates vinculin's head-tail interaction, unmasking its talin- and actin-binding sites. Microinjection of antibodies against PtdInsP2 inhibit assembly of stress fibres and focal adhesions.
纽蛋白是一种在细胞与底物黏附（黏着斑）和细胞间黏附（黏着连接）中起重要作用的细胞骨架蛋白，它与包括踝蛋白和肌动蛋白在内的其他细胞骨架蛋白相互作用。纽蛋白头部和尾部结构域之间的分子内相互作用掩盖了这两种蛋白的结合位点。隐藏结合位点的暴露对于促进黏着斑组装可能很重要。几种诱导黏着斑形成的因子通过GTP结合蛋白Rho起作用，Rho通过激活磷脂酰肌醇-4-磷酸-5-羟基激酶（磷脂酰肌醇-5-羟基激酶）来提高磷脂酰肌醇-4,5-二磷酸（PtdInsP2）的水平。PtdInsP2调节几种肌动蛋白结合蛋白，包括丝切蛋白、凝溶胶蛋白和α-辅肌动蛋白，并与纽蛋白相互作用。我们在此报告，PtdInsP2可使纽蛋白的头尾相互作用解离，从而暴露其与踝蛋白和肌动蛋白的结合位点。显微注射抗PtdInsP2抗体可抑制应力纤维和黏着斑的组装。
