Contact-dependent promotion of cell migration by the OL-protocadherin-Nap1 interaction.

Contact-dependent promotion of cell migration by the OL-protocadherin-Nap1 interaction.
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DOI:
10.1083/jcb.200802069
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发表时间:
2008-07-28
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Takeichi M
Takeichi M
中科院分区:
其他
文献类型:
--
作者:
Nakao S;Platek A;Hirano S;Takeichi M

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OL-原钙粘蛋白 (OL-pc) 是一种属于钙粘蛋白超家族的跨膜蛋白,已被证明通过其亲同性相互作用在细胞与细胞接触处积累,但其分子作用仍然难以捉摸。在这项研究中,我们发现 OL-pc 结合 Nck 相关蛋白 1 (Nap1),这是一种调节 WAVE 介导的肌动蛋白组装的蛋白。在不表达 OL-pc 的星形细胞瘤 U251 细胞中,Nap1 仅沿板状伪足定位。然而,这些细胞中 OL-pc 的外源表达将 Nap1 和 WAVE1 招募到细胞-细胞接触位点。尽管 OL-pc 表达对单独的 U251 细胞的运动没有影响,但当它们彼此接触时,它会加速它们的运动,导致细胞连接处的 F-肌动蛋白和 N-钙粘蛋白同时重组。缺乏 Nap1 结合位点的 OL-pc 突变体没有表现出这样的效果。 N-钙粘蛋白敲低模拟 OL-pc 表达,增强细胞运动。这些结果表明,OL-pc 通过将 Nap1-WAVE1 复合物招募到这些位点来重塑细胞连接处的运动性和粘附机制,进而促进细胞的迁移。
OL-protocadherin (OL-pc) is a transmembrane protein belonging to the cadherin superfamily, which has been shown to accumulate at cell–cell contacts via its homophilic interaction, but its molecular roles remain elusive. In this study, we show that OL-pc bound Nck-associated protein 1 (Nap1), a protein that regulates WAVE-mediated actin assembly. In astrocytoma U251 cells not expressing OL-pc, Nap1 was localized only along the lamellipodia. However, exogenous expression of OL-pc in these cells recruited Nap1 as well as WAVE1 to cell–cell contact sites. Although OL-pc expression had no effect on the motility of solitary U251 cells, it accelerated their movement when they were in contact with one another, causing concomitant reorganization of F-actin and N-cadherin at cell junctions. OL-pc mutants lacking the Nap1-binding site exhibited no such effect. N-cadherin knockdown mimicked OL-pc expression in enhancing cell movement. These results suggest that OL-pc remodels the motility and adhesion machinery at cell junctions by recruiting the Nap1–WAVE1 complex to these sites and, in turn, promotes the migration of cells.
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