Localization of LAT in glycolipid-enriched microdomains is required for T cell activation

LAT, a transmembrane adapter protein found in glycolipid-enriched microdoma ins (GEMs), is essential for T cell activation. In this study, we have util ized a LAT-deficient mutant of the Jurkat T cell line, J.CaM2, to explore v arious requirements for LAT function. First, we demonstrate that LAT must b e present in GEMs for coupling T cell receptor (TCR) engagement to activati on of the Ras signaling pathway, increases in intracellular Ca2+, and induc tion of the transcription factor nuclear factor of activated T cells (NF-AT ). Second, we show that the extracellular and transmembrane domains of LAT are dispensable for these TCR-mediated events once LAT has localized to GEM s. These results provide important insights into both the structural domain s of LAT and its subcellular localization that are required for effective T CR signaling.