Rab13 Small G Protein and Junctional Rab13-binding Protein (JRAB) Orchestrate Actin Cytoskeletal Organization during Epithelial Junctional Development
Rab13 Small G Protein and Junctional Rab13-binding Protein (JRAB) Orchestrate Actin Cytoskeletal Organization during Epithelial Junctional Development
复制标题
DOI：
10.1074/jbc.m112.383653
复制
发表时间：
2012-12-14
影响因子：
4.8
通讯作者：
Sasaki, Takuya
中科院分区：
文献类型：
--
作者：
Sakane, Ayuko;Abdallah, Ahmed Alamir Mahmoud;Sasaki, Takuya
在上皮细胞连接发育过程中，囊泡的运输和肌动蛋白细胞骨架的重组都必须受到时空调控。这些细胞功能的协调尤其重要，但确切的机制仍然难以捉摸。以前，我们发现与CASL-like 2相互作用的JRAb(JRAb)/分子(Mical-L2)是Rab13小G蛋白的效应器，并且我们发现Rab13-JRAb系统可能通过转运黏附分子参与细胞间黏附的形成。在这里，我们发现JRAb通过不同的结构域与两个肌动蛋白结合蛋白，肌动蛋白-1和肌动蛋白-4以及丝状肌动蛋白相互作用，并通过这些相互作用调节肌动蛋白的交联性和稳定性。在上皮连接发育过程中，JRAb在游离边界的肌动蛋白束中显著富含；随后，JRAb经历了依赖于Rab13的构象变化，这是细胞-细胞黏附位置成熟所必需的。这些结果表明，Rab13和JRAb调控着从细胞-细胞黏附的建立到成熟的整个上皮连接发育过程中肌动蛋白细胞骨架的重组。
During epithelial junctional development, both vesicle transport and reorganization of the actin cytoskeleton must be spatiotemporally regulated. Coordination of these cellular functions is especially important, but the precise mechanism remains elusive. Previously, we identified junctional Rab13-binding protein (JRAB)/molecules interacting with CasL-like 2 (MICAL-L2) as an effector of the Rab13 small G protein, and we found that the Rab13-JRAB system may be involved in the formation of cell-cell adhesions via transport of adhesion molecules. Here, we showed that JRAB interacts with two actin-binding proteins, actinin-1 and -4, and filamentous actin via different domains and regulates actin cross-linking and stabilization through these interactions. During epithelial junctional development, JRAB is prominently enriched in the actin bundle at the free border; subsequently, JRAB undergoes a Rab13-dependent conformational change that is required for maturation of cell-cell adhesion sites. These results suggest that Rab13 and JRAB regulate reorganization of the actin cytoskeleton throughout epithelial junctional development from establishment to maturation of cell-cell adhesion.