Kawakatsu Tomomi, Shimizu Kazuya, Honda Tomoyuki, Fukuhara Tatsuro, Hoshino Takashi, Takai Yoshimi
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
J Biol Chem. 2002 Dec 27;277(52):50749-55. doi: 10.1074/jbc.M209846200. Epub 2002 Oct 11.
Nectins and afadin constitute a novel cell-cell adhesion system that plays a cooperative role with cadherins in the organization of adherens junctions (AJs). Nectins are Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecules, and afadin is a nectin- and actin filament-binding protein that connects nectins to the actin cytoskeleton. Rac and Cdc42 small G proteins have been implicated in the organization of AJs, but their modes of action remain unknown. The trans-interaction of E-cadherin has recently been shown to induce the activation of Rac, but not that of Cdc42. We show here that the trans-interactions of nectins induce the formation of filopodia and lamellipodia through the respective activation of Cdc42 and Rac. The Cdc42 activation is necessary, but not sufficient, for the Rac-induced formation of lamellipodia, whereas the Rac activation is not necessary for the Cdc42-induced formation of filopodia. These effects of nectins require their cytoplasmic tail but not their association with afadin. We propose here the functional relationship between nectins and the small G proteins in the organization of AJs.
NECTIN蛋白和afadin蛋白构成了一种新型的细胞间黏附系统，该系统在黏着连接（AJs）的组织形成中与钙黏蛋白发挥协同作用。NECTIN蛋白是一类不依赖钙离子的免疫球蛋白样细胞间黏附分子，而afadin蛋白是一种能结合NECTIN蛋白和肌动蛋白丝的蛋白质，可将NECTIN蛋白与肌动蛋白细胞骨架相连。Rac和Cdc42小G蛋白参与了AJs的组织形成，但其作用方式尚不清楚。最近研究表明，E-钙黏蛋白的反式相互作用可诱导Rac激活，但不能诱导Cdc42激活。我们在此表明，NECTIN蛋白的反式相互作用通过分别激活Cdc42和Rac来诱导丝状伪足和片状伪足的形成。Cdc42激活对于Rac诱导的片状伪足形成是必要的，但并不充分，而Rac激活对于Cdc42诱导的丝状伪足形成并非必要。NECTIN蛋白的这些作用需要其胞质尾，但不需要其与afadin蛋白的结合。我们在此提出了NECTIN蛋白与小G蛋白在AJs组织形成中的功能关系。
