title: Development of nanoscale structure in LAT-based signaling complexes.
abstract: The adapter molecule linker for activation of T cells (LAT) plays a crucial role in forming signaling complexes induced by stimulation of the T cell receptor (TCR). These multi-molecular complexes are dynamic structures that activate highly regulated signaling pathways. Previously, we have demonstrated nanoscale structure in LAT-based complexes where the adapter SLP-76 (also known as LCP2) localizes to the periphery of LAT clusters. In this study, we show that initially LAT and SLP-76 are randomly dispersed throughout the clusters that form upon TCR engagement. The segregation of LAT and SLP-76 develops near the end of the spreading process. The local concentration of LAT also increases at the same time. Both changes require TCR activation and an intact actin cytoskeleton. These results demonstrate that the nanoscale organization of LAT-based signaling complexes is dynamic and indicates that different kinds of LAT-based complexes appear at different times during T cell activation.
authors.affiliation: Laboratory of Cellular and Molecular Biology, CCR, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Valarie A
authors.identifier: 0000-0001-5377-4753
authors.initials: VA
authors.lastname: Barr
authors.affiliation: Racah Institute of Physics, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Eilon
authors.identifier: 0000-0002-7403-6036
authors.initials: E
authors.lastname: Sherman
authors.affiliation: Laboratory of Cellular and Molecular Biology, CCR, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Jason
authors.identifier: 0000-0001-5131-6767
authors.initials: J
authors.lastname: Yi
authors.affiliation: Laboratory of Cellular and Molecular Biology, CCR, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Itoro
authors.identifier: 0000-0002-3239-6252
authors.initials: I
authors.lastname: Akpan
authors.affiliation: Laboratory of Cellular and Molecular Biology, CCR, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Alexandre K
authors.identifier: 0000-0003-2646-0040
authors.initials: AK
authors.lastname: Rouquette-Jazdanian
authors.affiliation: Laboratory of Cellular and Molecular Biology, CCR, NCI, NIH, Bethesda, MD 20892, USA samelsonl@helix.nih.gov.
authors.forename: Lawrence E
authors.identifier: 0000-0002-5963-2112
authors.initials: LE
authors.lastname: Samelson
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008560:Membrane Fluidity; D008565:Membrane Proteins / Q000378:metabolism*; D008853:Microscopy; D049329:Nanostructures / Q000737:chemistry*; D010750:Phosphoproteins / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C110810:LAT protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; C092947:SLP-76 signal Transducing adaptor proteins; D049452:Green Fluorescent Proteins
keywords: Microcluster; Nanostructure; Photoactivated localization microscopy; Signaling complex; Single-molecule localization microscopy; T cell activation