Functions and mode of action of novel regulatory systems for cell adhesion and motility

我们发现了一种新的细胞粘附调节系统。该系统由nectin和afadin组成。Nectin是一种免疫球蛋白样细胞粘附分子，afadin是一种F-肌动蛋白结合蛋白，连接Nectin和肌动蛋白细胞骨架，Nectin-afadin系统在上皮细胞中形成粘附和紧密连接，我们还发现了一种新的细胞运动调节系统。该系统由frabin和Cdc 42小G蛋白组成。Frabin是一种激活Cdc 42的F-肌动蛋白融合蛋白。在2000年至2001年的支持期间，我们研究了这些nectin-afadin和frabin-Cdc 42系统的功能和作用方式。结果如下：（1）上皮细胞中，nectin-afadin系统将cadherin-catenin和JAM-ZO-1系统募集到以nectin为基础的细胞间粘附位点。在神经元中，nectin-afadin系统定位于突触，参与突触信息的传递。在睾丸中，nectin-afadin系统参与Sertoli-精子细胞连接的形成，并对精子细胞的形态发生至关重要。(2)Frabin与特定的肌动蛋白和膜结构结合，不仅激活Cdc 42，而且激活这些结构附近的Rac小G蛋白，最终导致细胞运动。Frabin的F-肌动蛋白结合活性与Cdc 42激活活性在细胞运动中协同起作用。

We have found a novel regulatory system for cell adhesion. This system consists of nectin and afadin. Nectin is an immunoglobulin-like cell adhesion molecule, and afadin is an F-aotin-binding protein that connects nectin to the actin cytoskeleton.The nectin-afadin system organizes adherens and tight jjunctions in epithelial cells.We have also found a novel regulatory system for cell motility. This system consists of frabin and Cdc42 small G protein. Frabin is an F-actin-blnding protein that activates Cdc42. During this support from2000-to 2001, we have studied the functions and mode of action of these nectin-afadin and frabin-Cdc42 systems. The results obtained are as follows :(1) In epithelial cells, the nectin-afadin system recruits the cadherin-catenin and JAM-ZO-lsystems to nectin-based cell-cell adhesion sites. In neurons, the nectin-afadinsystemis localized at synapses and involved information of synapses. In testis, the nectin-afadin system is involved in formation of Sertoli-spermatid junctions and essential for spermatid morphogenesis.(2) Frabin associates with specific actin and membrane structures and activates not only Cdc42 and but also Rac small G protein in the vicinity of these structures, eventually to leading to cell motility. The F-actin-binding activity of frabin cooperatively functions with the Cdc42-activating activity in cell motility.