Vinculin acts as a sensor in lipid regulation of adhesion-site turnover
Vinculin acts as a sensor in lipid regulation of adhesion-site turnover
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DOI：
10.1242/jcs.01734
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发表时间：
2005-04-01
影响因子：
4
通讯作者：
Ziegler, WH
中科院分区：
文献类型：
--
作者：
Chandrasekar, I;Stradal, TEB;Ziegler, WH
细胞粘附位点的动力学控制着细胞的形态和运动。黏附现场的周转被认为取决于酸性磷脂磷脂肌醇-4,5-二磷酸（PIP2）的局部可用性，PIP2可以结合许多细胞黏附蛋白，如血管蛋白和talin，但这种相互作用的后果尚不清楚。为了研究磷脂与血管蛋白结合对黏附现场周转和细胞运动的意义，我们构建了一个突变体，血管蛋白- ld，缺乏酸性磷脂结合，但具有功能的肌动蛋白结合位点。通过光漂白后荧光恢复（FRAP）分析判断，在细胞中表达时，vinculin-LD很容易被招募到粘附位点，但细胞的扩散和迁移受到严重损害，并且pip2依赖性的粘附分解受到抑制。因此，如前所述，PIP2结合对血管蛋白的激活和募集不是必需的。相反，我们提出PIP2水平可以调节肌动蛋白细胞骨架粘附位点的解偶联，而血管蛋白则作为传感器发挥作用。
The dynamics of cell adhesion sites control cell morphology and motility. Adhesion-site turnover is thought to depend on the local availability of the acidic phospholipid phosphatidylinositol-4,5-bisphosphate (PIP2)- PIP2 can bind to many cell adhesion proteins such as vinculin and talin, but the consequences of this interaction are poorly understood. To study the significance of phospholipid binding to vinculin for adhesion-site turnover and cell motility, we constructed a mutant, vinculin-LD, deficient in acidic phospholipid binding yet with functional actinbinding sites. When expressed in cells, vinculin-LD was readily recruited to adhesion sites, as judged by fluorescence recovery after photobleaching (FRAP) analysis, but cell spreading and migration were strongly impaired, and PIP2-dependent disassembly of adhesions was suppressed. Thus, PIP2 binding is not essential for vinculin activation and recruitment, as previously suggested. Instead, we propose that PIP2 levels can regulate the uncoupling of adhesion sites from the actin cytoskeleton, with vinculin functioning as a sensor.