Author | Houmadi, Raïssa | |
Author | Guipouy, Delphine | |
Author | Rey-Barroso, Javier | |
Author | Vasconcelos, Zilton | |
Author | Cornet, Julie | |
Author | Manghi, Manoel | |
Author | Destainville, Nicolas | |
Author | Valitutti, Salvatore | |
Author | Allart, Sophie | |
Author | Dupré, Loïc | |
Access date | 2015-02-02T11:02:31Z | |
Available date | 2015-02-02T11:02:31Z | |
Document date | 2018 | |
Citation | HOUMADI, Raïssa et al. The Wiskott-Aldrich Syndrome Protein Contributes to the Assembly of the LFA-1 Nanocluster Belt at the Lytic Synapse. Cell Reports, v. 22, n. 4, p. 979-991, Jan. 2018. | pt_BR |
ISSN | 2211-1247 | |
URI | https://www.arca.fiocruz.br/handle/icict/9402 | |
Language | por | pt_BR |
Publisher | Cell Press | pt_BR |
Rights | open access | |
Title | The Wiskott-Aldrich Syndrome Protein Contributes to the Assembly of the LFA-1 Nanocluster Belt at the Lytic Synapse | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.celrep.2017.12.088 | |
Abstract | T lymphocyte cytotoxicity relies on a synaptic ring of lymphocyte function-associated antigen 1 (LFA-1), which permits polarized delivery of lytic granules. How LFA-1 organization is controlled by underlying actin cytoskeleton dynamics is poorly understood. Here, we explored the contribution of the actin cytoskeleton regulator WASP to the topography of LFA-1 using a combination of microscopy modalities. We uncover that the reduced cytotoxicity of Wiskott-Aldrich syndrome patient-derived CD8+ T lymphocytes lacking WASP is associated with reduced LFA-1 activation, unstable synapse, and delayed lethal hit. At the nanometric scale, WASP constrains high-affinity LFA-1 into dense nanoclusters located in actin meshwork interstices. At the cellular scale, WASP is required for the assembly of a radial belt composed of hundreds of LFA-1 nanoclusters and for lytic granule docking within this belt. Our study unravels the nanoscale topography of LFA-1 at the lytic synapse and identifies WASP as a molecule controlling individual LFA-1 cluster density and LFA-1 nanocluster belt integrity. | pt_BR |
Affilliation | INSERM, UMR 1043, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France / Université Toulouse III Paul Sabatier, Toulouse, France / CNRS, UMR 5282, Toulouse, France. | pt_BR |
Affilliation | INSERM, UMR 1043, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France / Université Toulouse III Paul Sabatier, Toulouse, France / CNRS, UMR 5282, Toulouse, France / TxCell, Allée de la Nertière, Valbonne, Sophia-Antipolis, France. | pt_BR |
Affilliation | INSERM, UMR 1043, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France / Université Toulouse III Paul Sabatier, Toulouse, France / CNRS, UMR 5282, Toulouse, France. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Université Toulouse III Paul Sabatier, Toulouse, France / CNRS, UMR 5152, Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes, Laboratoire de Physique Théorique, Toulouse, France. | pt_BR |
Affilliation | Université Toulouse III Paul Sabatier, Toulouse, France / CNRS, UMR 5152, Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes, Laboratoire de Physique Théorique, Toulouse, France. | pt_BR |
Affilliation | Université Toulouse III Paul Sabatier, Toulouse, France / CNRS, UMR 5152, Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes, Laboratoire de Physique Théorique, Toulouse, France. | |
Affilliation | INSERM, UMR 1043, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France / Université Toulouse III Paul Sabatier, Toulouse, France / CNRS, UMR 5282, Toulouse, France / Department of Pathology, Institut Universitaire du Cancer-Oncopole de Toulouse, Toulouse, France. | |
Affilliation | INSERM, UMR 1043, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France / Université Toulouse III Paul Sabatier, Toulouse, France / CNRS, UMR 5282, Toulouse, France. | |
Affilliation | INSERM, UMR 1043, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France / Université Toulouse III Paul Sabatier, Toulouse, France / CNRS, UMR 5282, Toulouse, France. | |
Subject | LFA-1 | |
Subject | Wiskott-Aldrich syndrome protein | |
Subject | Actin cytoskeleton | |
Subject | Cytotoxic T lymphocytes | |
Subject | Immunological synapse | |
Subject | Lytic granules | |
Subject | Super-resolution microscopy | |