A two-tiered mechanism for stabilization and immobilization of E-cadherin
A two-tiered mechanism for stabilization and immobilization of E-cadherin
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DOI：
10.1038/nature06953
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发表时间：
2008-06-05
期刊：
影响因子：
64.8
通讯作者：
Lecuit, Thomas
中科院分区：
文献类型：
--
作者：
Cavey, Matthieu;Rauzi, Matteo;Lecuit, Thomas
上皮组织保持稳健的结构，这对其屏障功能很重要，但它们也通过细胞-细胞接触的重组而重塑。组织稳定性需要由E-钙粘蛋白介导的细胞间粘附，特别是它在由肌动蛋白丝通过β-和α-连环蛋白支持的嗜同性复合物中的反式缔合. E-钙粘蛋白/β-连环蛋白和皮质肌动蛋白之间的α-连环蛋白动态相互作用如何控制粘附的稳定性和重塑尚不清楚。在这里，我们专注于果蝇嗜同性E-钙粘蛋白复合物，而不是总的E-钙粘蛋白，包括扩散的'自由' E-钙粘蛋白，因为这些复合物是一个更好的代理粘附。我们发现E-钙粘蛋白复合物在非常稳定的微区（即，真正的粘附灶比重塑接触更稳定）中分配。此外，我们发现，这些微域的稳定性和流动性取决于两个肌动蛋白群体：小，稳定的肌动蛋白补丁集中在嗜同性E-钙粘蛋白集群，而迅速翻转，收缩网络约束其横向运动的拴系机制。α-连环蛋白主要通过调节嗜同性簇的移动性来控制上皮结构，并且其稳定性在很大程度上受到限制。E-钙粘蛋白复合物的解偶联稳定性和流动性表明，稳定的上皮可能通过非常稳定的粘附灶的调节流动性来重塑。
Epithelial tissues maintain a robust architecture which is important for their barrier function, but they are also remodelled through the reorganization of cell - cell contacts. Tissue stability requires intercellular adhesion mediated by E- cadherin, in particular its trans- association in homophilic complexes supported by actin filaments through beta- and alpha- catenin. How alpha- catenin dynamic interactions between E- cadherin/ beta- catenin and cortical actin control both stability and remodelling of adhesion is unclear. Here we focus on Drosophila homophilic E- cadherin complexes rather than total E- cadherin, including diffusing 'free' E- cadherin, because these complexes are a better proxy for adhesion. We find that E- cadherin complexes partition in very stable microdomains ( that is, bona fide adhesive foci which are more stable than remodelling contacts). Furthermore, we find that stability and mobility of these microdomains depend on two actin populations: small, stable actin patches concentrate at homophilic E- cadherin clusters, whereas a rapidly turning over, contractile network constrains their lateral movement by a tethering mechanism. alpha- Catenin controls epithelial architecture mainly through regulation of the mobility of homophilic clusters and it is largely dispensable for their stability. Uncoupling stability and mobility of E- cadherin complexes suggests that stable epithelia may remodel through the regulated mobility of very stable adhesive foci.