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Immunity. 2011 Nov 23;35(5):705-20. doi: 10.1016/j.immuni.2011.10.004. Epub 2011 Nov 4.

Functional nanoscale organization of signaling molecules downstream of the T cell antigen receptor.

Author information

1
Laboratory of Cellular and Molecular Biology, CCR, NCI, NIH, Bethesda, MD 20892, USA.

Abstract

Receptor-regulated cellular signaling often is mediated by formation of transient, heterogeneous protein complexes of undefined structure. We used single and two-color photoactivated localization microscopy to study complexes downstream of the T cell antigen receptor (TCR) in single-molecule detail at the plasma membrane of intact T cells. The kinase ZAP-70 distributed completely with the TCRζ chain and both partially mixed with the adaptor LAT in activated cells, thus showing localized activation of LAT by TCR-coupled ZAP-70. In resting and activated cells, LAT primarily resided in nanoscale clusters as small as dimers whose formation depended on protein-protein and protein-lipid interactions. Surprisingly, the adaptor SLP-76 localized to the periphery of LAT clusters. This nanoscale structure depended on polymerized actin and its disruption affected TCR-dependent cell function. These results extend our understanding of the mechanism of T cell activation and the formation and organization of TCR-mediated signaling complexes, findings also relevant to other receptor systems.

PMID:
22055681
PMCID:
PMC3225724
DOI:
10.1016/j.immuni.2011.10.004
[Indexed for MEDLINE]
Free PMC Article

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