Endocytosis of E-cadherin regulated by Rac and Cdc42 small G proteins through IQGAP1 and actin filaments.

E-cadherin is a key cell–cell adhesion molecule at adherens junctions (AJs) and undergoes endocytosis when AJs are disrupted by the action of extracellular signals. To elucidate the mechanism of this endocytosis, we developed here a new cell-free assay system for this reaction using the AJ-enriched fraction from rat liver. We found here that non-trans-interacting, but not trans-interacting, E-cadherin underwent endocytosis in a clathrin-dependent manner. The endocytosis of trans-interacting E-cadherin was inhibited by Rac and Cdc42 small G proteins, which were activated by trans-interacting E-cadherin or trans-interacting nectins, which are known to induce the formation of AJs in cooperation with E-cadherin. This inhibition was mediated by reorganization of the actin cytoskeleton by Rac and Cdc42 through IQGAP1, an actin filament-binding protein and a downstream target of Rac and Cdc42. These results indicate the important role of the Rac/Cdc42-IQGAP1 system in the dynamic organization and maintenance of the E-cadherin–based AJs.

E - 钙黏蛋白是黏附连接（AJs）处关键的细胞 - 细胞黏附分子，当黏附连接因细胞外信号作用而被破坏时，它会发生内吞作用。为阐明这种内吞作用的机制，我们在此利用从大鼠肝脏中提取的富含黏附连接的组分，开发了一种用于该反应的新型无细胞检测系统。我们在此发现，非反式相互作用的E - 钙黏蛋白（而非反式相互作用的E - 钙黏蛋白）以网格蛋白依赖的方式发生内吞作用。反式相互作用的E - 钙黏蛋白的内吞作用受到Rac和Cdc42小G蛋白的抑制，这些小G蛋白可由反式相互作用的E - 钙黏蛋白或反式相互作用的 nectins激活，已知nectins会与E - 钙黏蛋白协同诱导黏附连接的形成。这种抑制是通过Rac和Cdc42经由IQGAP1（一种肌动蛋白丝结合蛋白，也是Rac和Cdc42的下游靶点）对肌动蛋白细胞骨架进行重组来介导的。这些结果表明Rac/Cdc42 - IQGAP1系统在基于E - 钙黏蛋白的黏附连接的动态组织和维持中具有重要作用。