Role of Rab13 binding protein JRAB/MICAL-L2 in regulating cell polarity and adhesion

上皮细胞连接的动态重排，紧密连接(TJ)和黏附连接(AJ)，是维持机体对各种刺激反应的动态平衡所必需的。完整的TJ和AJ蛋白、claudins、occludins和cadherins进入和/或从质膜转运使这种重排成为可能。我们先前发现Rab13和JRAb/Mical-L2(JRAb)介导了阻滞素的内吞循环。在本研究中，我们通过酵母双杂交筛选，鉴定了Rab8和Actinin-4为JRAB结合蛋白。Rab13和Rab8分别在质膜和循环内体上竞争JRAb结合，并在功能上与JRAb结合。此外，Rab13结合的JRAb通过与肌动蛋白-4的结合而靶向于质膜。这些结果表明，JRAb通过与Rab13、Rab8和Actinin-4结合来调节上皮细胞的极性和黏附。

Dynamic rearrangement of epithelial cell junctions, tight junction (TJ) and adherens junction (AJ), is essential to maintain the homeostasis of the organism in response to various stimuli. The transport of integral TJ and AJ proteins, claudins, occludins and cadherins, to and/or from the plasma membrane enables this rearrangement. We previously revealed that Rab13 and JRAB/MICAL-L2 (JRAB) mediated the endocytic recycling of occludin. In the present study, we identified Rab8 and actinin-4 as JRAB-binding proteins by using yeast two-hybrid screening. Rab13 and Rab8 competed with each other for the binding to JRAB and functionally associated with JRAB at the plasma membrane and recycling endosome, respectively. Furthermore, Rab13-bound JRAB was targeted to the plasma membrane through its binding to actinin-4. These results suggest that JRAB regulates epithelial cell polarity and adhesion through its binding to Rab13, Rab8 and actinin-4.