title: Functional nanoscale organization of signaling molecules downstream of the T cell antigen receptor.
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.
authors: Laboratory of Cellular and Molecular Biology, CCR, NCI, NIH, Bethesda, MD 20892, USA.
authors: Eilon
authors: E
authors: Sherman
authors: Valarie
authors: V
authors: Barr
authors: Suliana
authors: S
authors: Manley
authors: George
authors: G
authors: Patterson
authors: Lakshmi
authors: L
authors: Balagopalan
authors: Itoro
authors: I
authors: Akpan
authors: Carole K
authors: CK
authors: Regan
authors: Robert K
authors: RK
authors: Merrill
authors: Connie L
authors: CL
authors: Sommers
authors: Jennifer
authors: J
authors: Lippincott-Schwartz
authors: Lawrence E
authors: LE
authors: Samelson
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000276:immunology; D011485:Protein Binding; D055503:Protein Multimerization; D021381:Protein Transport; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C110810:LAT protein, human; D008565:Membrane Proteins; C113392:PALM protein, human; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; C092947:SLP-76 signal Transducing adaptor proteins; D051746:ZAP-70 Protein-Tyrosine Kinase; D051966:Phospholipase C gamma