Rac-WAVE-mediated actin reorganization is required for organization and maintenance of cell-cell adhesion
Rac-WAVE-mediated actin reorganization is required for organization and maintenance of cell-cell adhesion
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DOI：
10.1242/jcs.03311
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发表时间：
2006-12
影响因子：
4
通讯作者：
D. Yamazaki;Tsukasa Oikawa;T. Takenawa
中科院分区：
文献类型：
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作者：
D. Yamazaki;Tsukasa Oikawa;T. Takenawa
在钙粘蛋白依赖的细胞-细胞粘附过程中，上皮细胞中的肌动蛋白细胞骨架经历动态重组。Rho家族小GTP酶调节肌动蛋白动力学，在钙粘蛋白依赖的细胞-细胞粘附中起关键作用;然而，细胞-细胞粘附形成的确切分子机制仍不清楚。在这里，我们表明，Wiskott-Aldrich综合征蛋白家族verprolin同源蛋白（WAVE）介导的肌动蛋白重组，下游的Rac在MDCK细胞中的钙粘蛋白依赖性细胞-细胞粘附的正常发展中起着重要作用。RAC诱导的钙粘蛋白依赖性粘连的发展需要WAVE2依赖性肌动蛋白重组。细胞-细胞粘附的过程分为三个步骤：新的细胞-细胞接触的形成，这些新接触的稳定和连接成熟。WAVE 1和WAVE 2在MDCK细胞中表达。WAVE1和WAVE2的功能在该系统中是冗余的，但WAVE2似乎起着更重要的作用。在第一步中，WAVE2依赖性板状伪足突起促进细胞-细胞接触的形成。在第二步，WAVE2招募肌动蛋白丝到新的细胞-细胞接触和稳定新形成的钙粘蛋白簇。在第三步，WAVE2依赖的肌动蛋白重组所需的组织和维持成熟的细胞-细胞粘附。因此，Rac-WAVE依赖性肌动蛋白重组不仅参与细胞-细胞粘附的形成，而且也是维持细胞-细胞粘附所必需的。
During cadherin-dependent cell-cell adhesion, the actin cytoskeleton undergoes dynamic reorganization in epithelial cells. Rho-family small GTPases, which regulate actin dynamics, play pivotal roles in cadherin-dependent cell-cell adhesion; however, the precise molecular mechanisms that underlie cell-cell adhesion formation remain unclear. Here we show that Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE)-mediated reorganization of actin, downstream of Rac plays an important role in normal development of cadherin-dependent cell-cell adhesions in MDCK cells. Rac-induced development of cadherin-dependent adhesions required WAVE2-dependent actin reorganization. The process of cell-cell adhesion is divided into three steps: formation of new cell-cell contacts, stabilization of these new contacts and junction maturation. WAVE1 and WAVE2 were expressed in MDCK cells. The functions of WAVE1 and WAVE2 were redundant in this system but WAVE2 appeared to play a more significant role. During the first step, WAVE2-dependent lamellipodial protrusions facilitated formation of cell-cell contacts. During the second step, WAVE2 recruited actin filaments to new cell-cell contacts and stabilized newly formed cadherin clusters. During the third step, WAVE2-dependent actin reorganization was required for organization and maintenance of mature cell-cell adhesions. Thus, Rac-WAVE-dependent actin reorganization is not only involved in formation of cell-cell adhesions but is also required for their maintenance.