Transient protein accumulation at the center of the T cell antigen presenting cell interface drives efficient IL-2 secretion
| Autor: | Danielle J. Clark, Laura E. McMillan, Sin Lih Tan, Gaia Bellomo, Clémentine Massoué, Harry Thompson, Lidiya Mykhaylechko, Dominic Alibhai, Xiongtao Ruan, Kentner L. Singleton, Minna Du, Alan J. Hedges, Pamela L. Schwartzberg, Paul Verkade, Robert F. Murphy, Christoph Wülfing |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
biology Chemistry Effector T cell Cell CD28 Signal transducing adaptor protein 010402 general chemistry 01 natural sciences 0104 chemical sciences Cell biology 03 medical and health sciences medicine.anatomical_structure medicine biology.protein Secretion GRB2 Antigen-presenting cell 030304 developmental biology |
| DOI: | 10.1101/296616 |
| Popis: | Supramolecular signaling assemblies are of interest for their unique signaling properties. A µm scale signaling assembly, the central supramolecular signaling cluster (cSMAC), forms at the center of the interface of T cells activated by antigen presenting cells. We have determined that it is composed of multiple complexes of a supramolecular volume of up to 0.5µm3 and associated with extensive membrane undulations. To determine cSMAC function, we have systematically manipulated the localization of three adaptor proteins, LAT, SLP-76, and Grb2. cSMAC localization varied between the adaptors and was diminished upon blockade of the costimulatory receptor CD28 and deficiency of the signal amplifying kinase Itk. Reconstitution of cSMAC localization restored IL-2 secretion which is a key T cell effector function as dependent on reconstitution dynamics. Our data suggest that the cSMAC enhances early signaling by facilitating signaling interactions and attenuates signaling thereafter through sequestration of a more limited set of signaling intermediates. |
| Databáze: | OpenAIRE |
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