Pre-existing clusters of the adaptor Lat do not participate in early T cell signaling events

David J. Williamson, Dylan Owen, Jeremie Rossy, Astrid Magenau, Matthias Wehrmann, J. Justin Gooding, Katharina Gaus

Research output: Contribution to journalArticlepeer-review

250 Citations (Scopus)


Engaged T cell antigen receptors (TCRs) initiate signaling through the adaptor protein Lat. In quiescent T cells, Lat is segregated into clusters on the cell surface, which raises the question of how TCR triggering initiates signaling. Using super-resolution fluorescence microscopy, we found that pre-existing Lat domains were neither phosphorylated nor laterally transported to TCR activation sites, which suggested that these clusters do not participate in TCR signaling. Instead, TCR activation resulted in the recruitment and phosphorylation of Lat from subsynaptic vesicles. Studies of Lat mutants confirmed that recruitment preceded and was essential for phosphorylation and that both processes were independent of surface clustering of Lat. Our data suggest that TCR ligation preconditions the membrane for vesicle recruitment and bulk activation of the Lat signaling network.
Original languageEnglish
Pages (from-to)655-662
Number of pages8
JournalNature Immunology
Issue number7
Publication statusPublished - 1 Jul 2011


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