Protein 4.1R regulates cell migration and IQGAP1 recruitment to the leading edge
Protein 4.1R regulates cell migration and IQGAP1 recruitment to the leading edge
复制标题
DOI：
10.1242/jcs.083634
复制
发表时间：
2011-08-01
影响因子：
4
通讯作者：
Correas, Isabel
中科院分区：
文献类型：
--
作者：
Ruiz-Saenz, Ana;Kremer, Leonor;Correas, Isabel
在红细胞中，多功能蛋白4.1R稳定了血影蛋白-肌动蛋白网络，并将其锚定在质膜上。为了进一步研究4.1R在非红系细胞中的功能作用，我们分析了4.1R蛋白在细胞迁移中的作用。内源性4.1R的分布偏向于迁移细胞的前沿。外源4.1R亚型含有完整的膜结合结构域，持续定位于富含F-肌动蛋白的质膜延伸。沉默4.1R导致亚融合细胞中迁移的持续性丧失，以及移动到伤口中的细胞失去定向迁移。免疫共沉淀和下拉实验证实支架蛋白IQGAP1是蛋白4.1R的伙伴，并表明4.1R膜结合域参与了IQGAP1的结合。重要的是，我们证明了蛋白质4.1R是IQGAP1定位到细胞迁移到伤口前沿所必需的，而IQGAP1不是蛋白质4.1R定位所必需的。总体而言，我们的结果表明，蛋白4.1R在细胞迁移和支架蛋白IQGAP1向细胞前沿募集方面发挥了关键作用。
In red blood cells, multifunctional protein 4.1R stabilizes the spectrin-actin network and anchors it to the plasma membrane. To contribute to the characterization of functional roles of 4.1R in nonerythroid cells, we have analyzed the participation of protein 4.1R in cell migration. The distribution of endogenous 4.1R is polarized towards the leading edge of migrating cells. Exogenous 4.1R isoforms containing a complete membrane-binding domain consistently localized to plasma membrane extensions enriched in F-actin. Silencing of 4.1R caused the loss of persistence of migration in subconfluent cells and of directional migration in cells moving into a wound. Coimmunoprecipitation and pull-down assays identified the scaffold protein IQGAP1 as a partner for protein 4.1R and showed that the 4.1R membrane-binding domain is involved in binding IQGAP1. Importantly, we show that protein 4.1R is necessary for the localization of IQGAP1 to the leading edge of cells migrating into a wound, whereas IQGAP1 is not required for protein 4.1R localization. Collectively, our results indicate a crucial role for protein 4.1R in cell migration and in the recruitment of the scaffold protein IQGAP1 to the cell front.