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Multiple proteins mediate IQGAP1-stimulated cell migration

机译：多种蛋白质介导IQGAP1刺激的细胞迁移

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Cell migration, a highly complex physiological phenomenon that requires the co-ordinated and tightly regulated function of several proteins, is mediated by a number of signalling pathways. Elucidation of the molecular mechanisms of cell migration impacts our comprehension of numerous cell functions, ranging from development and immune surveillance to angiogenesis and metastasis. The scaffold protein IQGAP1, which binds multiple proteins and regulates their functions, promotes cell motility. Many of the IQGAP1 binding proteins have been implicated in cell migration. In this study, we employed a multifaceted strategy to identify proteins that contribute to IQGAP1-stimulated cell migration. Using specific IQGAP1 point mutant constructs, an interaction with actin was shown to be essential for IQGAP1 to increase cell migration. In contrast, eliminating the binding of Ca2+/calmodulin, but not Ca2+-free calmodulin, augmented the ability of IQGAP1 to stimulate cell migration. Consistent with these findings, selective inhibition of calmodulin function at the plasma membrane with a specific peptide inhibitor enhanced cell migration mediated by IQGAP1. Interestingly, immunofluorescence staining and confocal microscopy suggest that localization of Cdc42 at the leading edge is not necessary for maximal migration of epithelial cells. Coupled with the observations that Cdc42 and Rac1 contribute to IQGAP1-stimulated cell migration, these data suggest that IQGAP1 serves as a junction to integrate multiple signalling molecules to facilitate cell migration. (c) 2007 Elsevier Inc. All rights reserved.
机译：细胞迁移是一种高度复杂的生理现象，它需要多种蛋白质的协调和严格调节的功能，它是由许多信号传导途径介导的。阐明细胞迁移的分子机制会影响我们对多种细胞功能的理解，从发育和免疫监控到血管生成和转移。支架蛋白IQGAP1与多种蛋白结合并调节其功能，可促进细胞运动。许多IQGAP1结合蛋白与细胞迁移有关。在这项研究中，我们采用了多方面的策略来鉴定有助于IQGAP1刺激的细胞迁移的蛋白质。使用特定的IQGAP1点突变体构建体，表明与肌动蛋白的相互作用对于IQGAP1增加细胞迁移至关重要。相反，消除Ca2 + /钙调蛋白的结合而不是不含Ca2 +的钙调蛋白的结合增加了IQGAP1刺激细胞迁移的能力。与这些发现一致的是，用特异性肽抑制剂选择性抑制质膜上的钙调蛋白功能可增强IQGAP1介导的细胞迁移。有趣的是，免疫荧光染色和共聚焦显微镜表明，Cdc42在前缘的定位对于上皮细胞的最大迁移不是必需的。结合Cdc42和Rac1有助于IQGAP1刺激的细胞迁移的观察结果，这些数据表明IQGAP1充当整合多个信号分子以促进细胞迁移的结合点。 （c）2007 Elsevier Inc.保留所有权利。

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