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

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.