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Instal the new for apple Halo Recruit1/12/2024 ![]() ![]() Using chimeric LAT with an extracellular tag, we previously provided evidence that cell surface LAT is efficiently recruited to microclusters, becomes phosphorylated, and propagates signals downstream of the TCR 10. The evidence for the first model involving plasma membrane-resident LAT comes from transmission electron microscopy (TEM) and super-resolution photoactivated localization microscopy (PALM) studies that propose that cell surface LAT is pre-clustered at the plasma membrane and cluster sizes increase upon T-cell stimulation 7– 9. In one model, direct recruitment of cell surface LAT to microclusters is critical for T-cell activation 7– 10, while in another model, vesicular, but not cell surface LAT, is essential 11– 14. There are two very different points of view regarding which LAT pool is recruited to microclusters and participates in TCR signaling. The relative importance of plasma membrane-localized LAT versus vesicular LAT for TCR signal transduction is a subject of active debate. LAT is localized at the plasma membrane and also in intracellular vesicles in resting and stimulated cells 5, 6. However, the critical sequence of events by which T cells establish signaling microclusters is unclear. Microclusters form within seconds of TCR engagement and are the basic signaling units required for T-cell activation. Microscopy studies have identified that T-cell engagement results in the rapid formation of microclusters containing many signaling molecules 3, 4. ![]() The phosphorylated tyrosines on LAT are nucleation sites for adapters and important signaling complexes that together mediate T-cell activation 2. Several studies in cell lines and mice have established the central importance of LAT in TCR signaling. Activated ZAP-70 phosphorylates linker for activation of T cells (LAT), a transmembrane adapter protein essential for T-cell signaling. ZAP-70, a second tyrosine kinase, is recruited from the cytosol to the phosphorylated receptor and in turn is phosphorylated and fully activated by Lck 1. ![]() Engagement of the TCR by a peptide-bound major histocompatibility complex (pMHC) molecule results in the phosphorylation of the signal transducing CD3 and TCRζ chains by the Src family kinase Lck. T cells express T-cell receptors (TCR) on their surface that bind and detect antigens. ![]()
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