Epithelial junction formation requires confinement of Cdc42 activity by a novel SH3BP1 complex.
Epithelial junction formation requires confinement of Cdc42 activity by a novel SH3BP1 complex.
复制标题
DOI：
10.1083/jcb.201202094
复制
发表时间：
2012-08-20
期刊：
影响因子：
--
通讯作者：
Balda MS
中科院分区：
文献类型：
--
作者：
Elbediwy A;Zihni C;Terry SJ;Clark P;Matter K;Balda MS
上皮连接的形成和形态发生需要GTP酶激活蛋白SH 3BP 1和F-肌动蛋白加帽蛋白CapZ来引导Cdc 42信号传导和细胞骨架动力学。上皮细胞-细胞粘附和形态发生需要肌动蛋白驱动的膜重塑的动态控制。Rho鸟苷三磷酸酶（GTdR）Cdc 42在细胞-细胞连接形成过程中调节连续的分子过程;因此，必须存在以时间和空间控制的方式抑制Cdc 42的机制。在本文中，我们使用功能性小干扰核糖核酸筛选确定SH 3BP 1（一种Cdc 42和Rac的GT酶激活蛋白）是连接组装和上皮形态发生的调节因子。SH 3BP 1的耗竭导致Cdc 42活性的空间控制丧失，膜重塑停滞，丝状伪足的生长增强。SH 3BP 1与JACOP/paracingulin（一种连接接头）和CD 2AP（一种支架蛋白）形成复合物;两者都是正常Cdc 42信号传导和连接形成所需的。丝状肌动蛋白帽蛋白CapZ也与SH 3BP 1复合物相关，并且是控制肌动蛋白重塑所必需的。因此，上皮连接的形成和形态发生需要一个双活性复合物，含有SH 3BP 1和CapZ，被招募到活性膜重塑的位点，以指导Cdc 42信号传导和细胞骨架动力学。
Epithelial junction formation and morphogenesis requires the GTPase-activating protein SH3BP1 and the F-actin–capping protein CapZ to guide Cdc42 signaling and cytoskeletal dynamics. Epithelial cell–cell adhesion and morphogenesis require dynamic control of actin-driven membrane remodeling. The Rho guanosine triphosphatase (GTPase) Cdc42 regulates sequential molecular processes during cell–cell junction formation; hence, mechanisms must exist that inactivate Cdc42 in a temporally and spatially controlled manner. In this paper, we identify SH3BP1, a GTPase-activating protein for Cdc42 and Rac, as a regulator of junction assembly and epithelial morphogenesis using a functional small interfering ribonucleic acid screen. Depletion of SH3BP1 resulted in loss of spatial control of Cdc42 activity, stalled membrane remodeling, and enhanced growth of filopodia. SH3BP1 formed a complex with JACOP/paracingulin, a junctional adaptor, and CD2AP, a scaffolding protein; both were required for normal Cdc42 signaling and junction formation. The filamentous actin–capping protein CapZ also associated with the SH3BP1 complex and was required for control of actin remodeling. Epithelial junction formation and morphogenesis thus require a dual activity complex, containing SH3BP1 and CapZ, that is recruited to sites of active membrane remodeling to guide Cdc42 signaling and cytoskeletal dynamics.
登录
查看更多内容
影响因子：
5.3
作者：
Hamann, Michael J.;Lubking, Casey M.;Billadeau, Daniel D.
通讯作者：
Billadeau, Daniel D.
影响因子：
5.3
作者：
Daubon, Thomas;Buccione, Roberto;Genot, Elisabeth
通讯作者：
Genot, Elisabeth
影响因子：
64.8
作者：
Billuart, P;Bienvenu, T;Chelly, J
通讯作者：
Chelly, J
DOI：
10.1016/s0006-291x(02)02645-1
发表时间：
2002-12-06
影响因子：
3.1
作者：
Komai, K;Okayama, R;Shiozawa, S
通讯作者：
Shiozawa, S
通过表达突变型紧密连接膜蛋白，细胞旁通透性和跨上皮电阻的功能性分离以及顶端-基底外侧膜内扩散屏障的破坏。
影响因子：
7.8
作者：
Balda, M S;Whitney, J A;Flores, C;Gonzalez, S;Cereijido, M;Matter, K
通讯作者：
Matter, K