Sorting Nexin 27 Enables MTOC and Secretory Machinery Translocation to the Immune Synapse
| العنوان: | Sorting Nexin 27 Enables MTOC and Secretory Machinery Translocation to the Immune Synapse |
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| المؤلفون: | Natalia González-Mancha, Cristina Rodríguez-Rodríguez, Andrés Alcover, Isabel Merida |
| المساهمون: | JEANNOT, FLORENCE, Innovative doctoral programme for talented early-stage researchers in Spanish host organisations excellent in the areas of Science, Technology, Engineering and Mathematics (STEM). H2020-EU.1.3.4 - INPhINIT - 713673 - INCOMING, Centro Nacional de Biotecnología [Madrid] (CNB-CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), NG-M received funding from the European Union Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement 713673 and 'La Caixa' Foundation (ID 100010434), with the fellowship code being LCF/BQ/DI17/11620027, as well as an EMBO short-term fellowship. CR-R held a predoctoral fellow of the Álvaro Entrecanales and Jérôme Lejeune Foundations. Research in IM’s lab is funded by grants from the Spanish Association Against Cancer (AECC, CICPF18), Aplastic Anemia and MDS International Foundation (AAMDSIF, OPE01644), Spanish Ministry of Science and Innovation (PID2019-108357RB-100/AEI/10.13039/501100011033), and the Madrid regional government (IMMUNOTHERCAM Consortium S2010/BMD-2326) to IM. Research in AA’s lab is funded by the French Ligue Nationale Contre le Cancer, Equipe Labellisée 2018)., European Project: 713673,INPhINIT |
| المصدر: | Frontiers in Immunology, Vol 12 (2022) Frontiers in Immunology Frontiers in Immunology, 2022, 12, pp.814570. ⟨10.3389/fimmu.2021.814570⟩ |
| بيانات النشر: | Frontiers Media S.A., 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Diacylglycerol Kinase, Immunological Synapses, T-Lymphocytes, [SDV]Life Sciences [q-bio], Immunology, diacylglycerol kinase z, Vesicular Transport Proteins, T lymphocytes, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Lymphocyte Activation, Models, Biological, immune response, Diglycerides, Jurkat Cells, Cell Line, Tumor, Immunology and Allergy, Humans, Sorting Nexins, SNX27, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Original Research, polarization, Secretory Pathway, Biological Transport, RC581-607, [SDV] Life Sciences [q-bio], centrosome, Protein Biosynthesis, Cytokines, diacylglycerol kinase ζ, Immunologic diseases. Allergy, retromer, Microtubule-Organizing Center, Signal Transduction |
| الوصف: | Sorting nexin 27 (SNX27) association to the retromer complex mediates intracellular trafficking of cargoes containing PSD95/Dlg1/ZO-1 (PDZ)-binding C-terminal sequences from endosomes to the cell surface, preventing their lysosomal degradation. Antigen recognition by T lymphocyte leads to the formation of a highly organized structure named the immune synapse (IS), which ensures cell-cell communication and sustained T cell activation. At the neuronal synapse, SNX27 recycles PDZ-binding receptors and its defective expression is associated with synaptic dysfunction and cognitive impairment. In T lymphocytes, SNX27 was found localized at recycling endosomal compartments that polarized to the IS, suggesting a function in polarized traffic to this structure. Proteomic analysis of PDZ-SNX27 interactors during IS formation identify proteins with known functions in cytoskeletal reorganization and lipid regulation, such as diacylglycerol (DAG) kinase (DGK) ζ, as well as components of the retromer and WASH complex. In this study, we investigated the consequences of SNX27 deficiency in cytoskeletal reorganization during IS formation. Our analyses demonstrate that SNX27 controls the polarization towards the cell-cell interface of the PDZ-interacting cargoes DGKζ and the retromer subunit vacuolar protein sorting protein 26, among others. SNX27 silencing abolishes the formation of a DAG gradient at the IS and prevents re-localization of the dynactin complex component dynactin-1/p150Glued, two events that correlate with impaired microtubule organizing center translocation (MTOC). SNX27 silenced cells show marked alteration in cytoskeleton organization including a failure in the organization of the microtubule network and defects in actin clearance at the IS. Reduced SNX27 expression was also found to hinder the arrangement of signaling microclusters at the IS, as well as the polarization of the secretory machinery towards the antigen presenting cells. Our results broaden the knowledge of SNX27 function in T lymphocytes by showing a function in modulating IS organization through regulated trafficking of cargoes. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::237acad2b19d931d5c82451331b23507Test https://www.frontiersin.org/articles/10.3389/fimmu.2021.814570/fullTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....237acad2b19d931d5c82451331b23507 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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