A network of PDZ-containing proteins regulates T cell polarity and morphology during migration and immunological synapse formation

A network of PDZ-containing proteins regulates T cell polarity and morphology during migration and immunological synapse formation
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DOI:
10.1016/j.immuni.2005.04.009
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发表时间:
2005-06-01
期刊:
影响因子:
32.4
通讯作者:
Russell, SM
Russell, SM
中科院分区:
医学1区
文献类型:
--
作者:
Ludford-Menting, MJ;Oliaro, J;Russell, SM

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T细胞的形状是由分子选择性地募集到细胞的不同区域(极性)决定的,它是T细胞功能的各个方面所不可或缺的,从迁移到细胞毒性。本研究描述了一种调节T细胞极性的机制。我们发现T细胞包含一个不对称分布的蛋白质网络,能够决定T细胞中细胞表面受体和形态决定因素的亚细胞定位。来自Scribble、Crums3和Par3复合体的蛋白质,以前被证明调节上皮极性,在含有尾足类或免疫突触的T细胞中被极化。Scribble表达的减少阻止了细胞表面受体的极化,并防止了与尾足形成、迁移和抗原呈递相关的形态变化。通过动态协调分子在T细胞中的分布,这个网络提供了一种机制,通过这种机制将T细胞的功能和极性联系在一起。
T cell shape is dictated by the selective recruitment of molecules to different regions of the cell (polarity) and is integral to every aspect of T cell function, from migration to cytotoxicity. This study describes a mechanism for the regulation of T cell polarity. We show that T cells contain a network of asymmetrically distributed proteins with the capacity to dictate the subcellular localization of both cell surface receptors and morphological determinants in T cells. Proteins from the Scribble, Crumbs3, and Par3 complexes, previously shown to regulate epithelial polarity, were polarized in T cells containing either uropods or immunological synapses. Reduction in Scribble expression prevented the polarization of cell surface receptors and prevented morphological changes associated with uropod formation, migration, and antigen presentation. By dynamically coordinating molecular distribution throughout the T cell, this network provides a mechanism by which T cell function and polarity are linked.