Gaidos Gabriel, Soni Shefali, Oswald Duane J, Toselli Paul A, Kirsch Kathrin H
Department of Biochemistry, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
J Cell Sci. 2007 Jul 15;120(Pt 14):2366-77. doi: 10.1242/jcs.004333.
Members of the CMS/CIN85 protein family participate in clathrin-mediated endocytosis and play a crucial role in maintaining the kidney filtration barrier. The CMS protein structure includes three Src homology 3 (SH3) domains and a proline-rich (PR) region that is connected by a 'linker' sequence to a coiled-coil (CC) domain. We show that CMS is a component of special actin-rich adhesion structures--podosomes--and demonstrate specific actin-binding properties of CMS. We have found that the entire C-terminal half of CMS is necessary for efficient binding to filamentous actin (F-actin). CMS and CIN85 can crosslink F-actin into bundles, a function that depends on the PR region and the CC domain. Removal of these domains reduces migration. CMS can also form heterotypic complexes with CIN85. CIN85 is expressed as multiple isoforms that share the CC domain, suggesting that heterotypic interactions with CMS provides a mechanism to regulate CMS binding to F-actin and thus for modulating dynamic rearrangements of the cytoskeleton.
CMS/CIN85蛋白家族成员参与网格蛋白介导的内吞作用，并在维持肾脏滤过屏障中发挥关键作用。CMS蛋白结构包括三个Src同源结构域3（SH3）和一个富含脯氨酸的（PR）区域，该区域通过一个“连接子”序列与一个卷曲螺旋（CC）结构域相连。我们发现CMS是富含肌动蛋白的特殊黏附结构——足体的一个组成部分，并证明了CMS具有特定的肌动蛋白结合特性。我们发现CMS的整个C端一半对于有效结合丝状肌动蛋白（F-肌动蛋白）是必需的。CMS和CIN85可以将F-肌动蛋白交联成束，这一功能依赖于PR区域和CC结构域。去除这些结构域会减少迁移。CMS还可以与CIN85形成异型复合物。CIN85以多种异构体形式表达，它们共享CC结构域，这表明与CMS的异型相互作用提供了一种调节CMS与F-肌动蛋白结合的机制，从而调节细胞骨架的动态重排。
