Departments of Biomedical Science, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK.
J Cell Sci. 2010 Jan 1;123(Pt 1):118-27. doi: 10.1242/jcs.047902.
Dystroglycan is a ubiquitously expressed cell adhesion protein. Its principal role has been determined as a component of the dystrophin-glycoprotein complex of muscle, where it constitutes a key component of the costameric cell adhesion system. To investigate more fundamental aspects of dystroglycan function in cell adhesion, we examined the role of dystroglycan in the dynamics and assembly of cellular adhesions in myoblasts. We show that beta-dystroglycan is recruited to adhesion structures and, based on staining for vinculin, that overexpression or depletion of dystroglycan affects both size and number of fibrillar adhesions. Knockdown of dystroglycan increases the size and number of adhesions, whereas overexpression decreases the number of adhesions. Dystroglycan knockdown or overexpression affects the ability of cells to adhere to different substrates, and has effects on cell migration that are consistent with effects on the formation of fibrillar adhesions. Using an SH3 domain proteomic screen, we identified vinexin as a binding partner for dystroglycan. Furthermore, we show that dystroglycan can interact indirectly with vinculin by binding to the vinculin-binding protein vinexin, and that this interaction has a role in dystroglycan-mediated cell adhesion and spreading. For the first time, we also demonstrate unequivocally that beta-dystroglycan is a resident of focal adhesions.
肌聚糖蛋白是一种普遍表达的细胞黏附蛋白。其主要功能是作为肌肉中肌营养不良糖蛋白复合物的组成部分，构成细胞黏附系统的重要组成部分。为了研究肌聚糖蛋白在细胞黏附中更基本的功能，我们研究了肌聚糖蛋白在成肌细胞黏附结构的动态和组装中的作用。我们发现β-肌聚糖蛋白被募集到黏附结构上，根据对粘着斑蛋白（vinculin）的染色，表明肌聚糖蛋白的过表达或缺失会影响纤维状黏附的大小和数量。肌聚糖蛋白的敲低会增加黏附的大小和数量，而过表达则会减少黏附的数量。肌聚糖蛋白的敲低或过表达会影响细胞黏附到不同基质的能力，并对细胞迁移产生影响，这与纤维状黏附的形成一致。通过使用 SH3 结构域蛋白质组筛选，我们鉴定出 vinexin 是肌聚糖蛋白的结合伴侣。此外，我们还表明，肌聚糖蛋白可以通过与粘着斑蛋白结合蛋白 vinexin 间接与粘着斑蛋白相互作用，并且这种相互作用在肌聚糖蛋白介导的细胞黏附和扩散中起作用。我们首次明确证明β-肌聚糖蛋白也是粘着斑的组成部分。
