The Par polarity complex regulates Rap1-and chemokine-induced T cell polarization

被引:101
作者
Gerard, Audrey [1 ]
Mertens, Alexander E. E. [1 ]
van der Kammen, Rob A. [1 ]
Collard, John G. [1 ]
机构
[1] Netherlands Canc Inst, Div Cell Biol, NL-1066 CX Amsterdam, Netherlands
关键词
D O I
10.1083/jcb.200608161
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:863 / 875
页数:13
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