The LIM protein Ajuba is recruited to cadherin-dependent cell junctions through an association with α-catenin

The LIM protein Ajuba is recruited to cadherin-dependent cell junctions through an association with α-catenin
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DOI:
10.1074/jbc.m205391200
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发表时间:
2003-01-10
影响因子:
4.8
通讯作者:
Braga, VMM
Braga, VMM
中科院分区:
生物学2区
文献类型:
--
作者:
Marie, H;Pratt, SJ;Braga, VMM

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细胞-细胞粘附事件影响细胞生长和命运决定,并为组织内的细胞极性提供空间线索。粘附点形成所需的完整分子决定因素及其功能尚未完全了解。含有LIM结构域的蛋白质已被证明存在于细胞-细胞接触位点,并且已知穿梭进入细胞核,在那里它们可以影响细胞命运和生长;然而,它们在细胞-细胞接触处的精确定位,它们如何定位于这些位点,以及它们在这些位点的功能是什么尚不清楚。在这里,我们表明,在原代角质形成细胞中,LIM结构域蛋白Ajuba以受调节的方式被募集到钙粘蛋白依赖性细胞-细胞粘附复合物中。在钙粘蛋白粘附复合物中,筋骨草与α-连环蛋白相互作用,并且α-连环蛋白是筋骨草有效募集到细胞连接处所必需的。Ajuba也直接与F-actin相互作用。来自Ajuba null小鼠的角质形成细胞表现出异常的细胞-细胞连接形成和/或稳定性和功能。这些数据揭示了在钙粘蛋白介导的细胞-细胞连接的一个新的组成部分,并建议,筋骨草可能有助于桥接的钙粘蛋白粘附复合物的肌动蛋白细胞骨架,并因此有助于形成或加强钙粘蛋白介导的细胞-细胞粘附。
Cell-cell adhesive events affect cell growth and fate decisions and provide spatial clues for cell polarity within tissues. The complete molecular determinants required for adhesive junction formation and their function are not completely understood. LIM domain-containing proteins have been shown to be present at cell-cell contact sites and are known to shuttle into the nucleus where they can affect cell fate and growth; however, their precise localization at cell-cell contacts, how they localize to these sites, and what their functions are at these sites is unknown. Here we show that, in primary keratinocytes, the LIM domain protein Ajuba is recruited to cadherin-dependent cell-cell adhesive complexes in a regulated manner. At cadherin adhesive complexes Ajuba interacts with a-catenin, and a-catenin is required for efficient recruitment of Ajuba to cell junctions. Ajuba also interacts directly with F-actin. Keratinocytes from Ajuba null mice exhibit abnormal cell-cell junction formation and/or stability and function. These data reveal Ajuba as a new component at cadherin-mediated cell-cell junctions and suggest that Ajuba may contribute to the bridging of the cadherin adhesive complexes to the actin cytoskeleton and as such contribute to the formation or strengthening of cadherin-mediated cell-cell adhesion.