The Par polarity complex regulates Rap1- and chemokine-induced T cell polarization.
The Par polarity complex regulates Rap1- and chemokine-induced T cell polarization.
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DOI：
10.1083/jcb.200608161
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发表时间：
2007-03-12
影响因子：
7.8
通讯作者：
Collard, John G
中科院分区：
文献类型：
--
作者：
Gerard, Audrey;Mertens, Alexander E E;van der Kammen, Rob A;Collard, John G
细胞极化是T细胞几乎所有功能所必需的，包括响应趋化因子的跨内皮迁移。然而，建立T细胞极性的分子途径知之甚少。我们发现，分区缺陷（Par）极性复合物的激活是Rap1和趋化因子诱导的T细胞极化过程中的一个关键事件。Par复合物的细胞内定位和激活由Rap1启动，并需要Cdc42活性。Rac激活剂Tiam 1与Rap 1和Par复合物的组分结合，从而可能起到将Par极性复合物与Rap 1连接并调节T细胞极化所需的Rac介导的肌动蛋白重塑的作用。与这些发现一致，Tiam1缺陷型T细胞在Rap1和趋化因子诱导的极化和趋化性中受损。我们的研究表明Tiam 1和Par极性复合物参与了T细胞的极化，并提供了趋化因子和Rap1调节T细胞极化和趋化性的机制。
Cell polarization is required for virtually all functions of T cells, including transendothelial migration in response to chemokines. However, the molecular pathways that establish T cell polarity are poorly understood. We show that the activation of the partitioning defective (Par) polarity complex is a key event during Rap1- and chemokine-induced T cell polarization. Intracellular localization and activation of the Par complex are initiated by Rap1 and require Cdc42 activity. The Rac activator Tiam1 associates with both Rap1 and components of the Par complex, and thereby may function to connect the Par polarity complex to Rap1 and to regulate the Rac-mediated actin remodelling required for T cell polarization. Consistent with these findings, Tiam1-deficient T cells are impaired in Rap1- and chemokine-induced polarization and chemotaxis. Our studies implicate Tiam1 and the Par polarity complex in polarization of T cells, and provide a mechanism by which chemokines and Rap1 regulate T cell polarization and chemotaxis.