A novel role of nectins in inhibition of the e-cadherin-induced activation of Rac and formation of cell-cell adherens junctions
A novel role of nectins in inhibition of the e-cadherin-induced activation of Rac and formation of cell-cell adherens junctions
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DOI：
10.1091/mbc.e03-05-0321
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发表时间：
2004-03-01
影响因子：
3.3
通讯作者：
Takai, Y
中科院分区：
文献类型：
--
作者：
Hoshino, T;Shimizu, K;Takai, Y
Nectin 是一种不依赖 Ca2+ 的免疫球蛋白 (Ig) 样细胞间粘附分子。 nectin 的反式相互作用将钙粘蛋白募集到基于 nectin 的细胞间粘附上，导致上皮细胞和成纤维细胞中细胞间粘附连接 (AJ) 的形成。 E-钙粘蛋白的反式相互作用诱导Rac小G蛋白的激活，而nectins的反式相互作用不仅诱导Rac而且还诱导Cdc42小G蛋白的激活。我们通过荧光共振能量转移（FRET）成像表明，E-钙粘蛋白的反式相互作用诱导Rac的动态激活和失活，从而导致板状伪足的动态形成和收缩。此外，我们在这里发现，不与其他nectin（非反式相互作用nectin）反式相互作用的nectin抑制了E-钙粘蛋白诱导的Rac激活，并降低了基于E-钙粘蛋白的细胞间AJ的形成速度。非反式相互作用nectin 的抑制作用被nectin 反式相互作用诱导的Cdc42 激活所抑制。这些结果表明 nectin 在调节 E-钙粘蛋白诱导的 Rac 激活和细胞间 AJ 形成中的新作用。
Nectins are Ca2+-independent immunoglobulin (Ig)-like cell-cell adhesion molecules. The trans-interactions of nectins recruit cadherins to the nectin-based cell-cell adhesion, resulting in formation of cell-cell adherens junctions (AJs) in epithelial cells and fibroblasts. The trans-interaction of E-cadherin induces activation of Rac small G protein, whereas the trans-interactions of nectins induce activation of not only Rac but also Cdc42 small G protein. We showed by the fluorescent resonance energy transfer (FRET) imaging that the trans-interaction of E-cadherin induced dynamic activation and inactivation of Rac, which led to dynamic formation and retraction of lamellipodia. Moreover, we found here that the nectins, which did not trans-interact with other nectins (non-trans-interacting nectins), inhibited the E-cadherin-induced activation of Rac and reduced the velocity of the formation of the E-cadherin-based cell-cell AJs. The inhibitory effect of non-trans-interacting nectins was suppressed by the activation of Cdc42 induced by the trans-interactions of nectins. These results indicate a novel role of nectins in regulation of the E-cadherin-induced activation of Rac and formation of cell-cell AJs.