Localization in vesicles, clusters and supramolecular complexes as key elements of LAT function

Laura E. McMillan, C. Wülfing
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Abstract

Linker for activation of T cells (LAT) is a central adaptor protein in proximal T cell activation. A key element of its adaptor function is the efficiency with which LAT interacts with its binding partners. Such efficiency is controlled by the local concentration of LAT as well as the vicinity to up- and downstream interaction partners, i.e. LAT localization. Several factors control LAT localization. LAT is a palmitoylated transmembrane protein and traffics between vesicular compartments and the plasma membrane. Membrane heterogeneity and protein-protein interactions can drive LAT clustering, at scales from a few to hundreds if not more molecules. LAT vesicular trafficking through the small, crowded cytoplasm of a T cell and the commonly nm scale clusters are difficult to access experimentally, in particular in the physiological interaction of T cells binding to antigen presenting cells (APCs) with a highly undulating interface. Only in recent years have technological advances begun to provide better access. Based on such advances, three elements of LAT localization are discussed in conjunction: vesicular trafficking as it regulates LAT transport towards, insertion into, and removal from the plasma membrane; LAT clustering as it increases local LAT concentrations; LAT-anchored supramolecular signaling complexes as they embed LAT in a dense network of interaction partners. Consistent with the important role of LAT localization for its function, each of these processes regulates LAT activity and the efficiency of T cell activation.
定位于囊泡、簇和超分子复合物是LAT功能的关键要素
T细胞活化连接子(Linker for activation of T cells, LAT)是近端T细胞活化的中心接头蛋白。其适配器功能的一个关键要素是LAT与其绑定伙伴交互的效率。这种效率受局部LAT浓度以及上下游相互作用伙伴附近的控制,即LAT局域化。有几个因素控制着LAT定位。LAT是一种棕榈酰化的跨膜蛋白,在囊室和质膜之间运输。膜的非均质性和蛋白质之间的相互作用可以驱动LAT聚集,从几个到数百个甚至更多的分子。LAT通过T细胞小而拥挤的细胞质和通常纳米级的团簇进行囊泡运输在实验上是困难的,特别是在T细胞与抗原提呈细胞(APCs)结合的生理相互作用中具有高度波动的界面。直到最近几年,技术进步才开始提供更好的途径。基于这些进展,本文结合讨论了LAT定位的三个要素:囊泡运输,因为它调节LAT向质膜的运输、插入和从质膜中移除;LAT聚集增加了局部LAT浓度;laat锚定的超分子信号复合物,因为它们将LAT嵌入相互作用伙伴的密集网络中。与LAT定位对其功能的重要作用一致,这些过程中的每一个都调节LAT活性和T细胞活化的效率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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