Protein Kinase C δ Regulates the Depletion of Actin at the Immunological Synapse Required for Polarized Exosome Secretion by T Cells
| Autor: | Jesús Gómez, Gonzalo Herranz, Alberto Fraile-Ramos, David Fernández-Moreno, Laura Márquez-Expósito, Sergio Dávila, Mario Quintanilla, Victor Calvo, Raúl de Martín, Pablo Aguilera, Alicia Sánchez, Manuel Izquierdo, Bianca Stancu, Ana Bello-Gamboa, Pablo Rodríguez-Silvestre, Teresa Fernández |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), European Commission, UAM. Departamento de Bioquímica |
| Rok vydání: | 2019 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
Cell death Medicina Endosome protein kinase C δ T-Lymphocytes Immunology Endocytic cycle Receptors Antigen T-Cell T lymphocytes Apoptosis macromolecular substances Lymphocyte Activation Exosomes Exosome Immune synapse Immunological synapse Jurkat Cells Cell Line Tumor Humans Immunology and Allergy Secretion RNA Small Interfering Protein kinase C Original Research cytotoxic activity Diacylglycerol kinase Multivesicular bodies Cytotoxic activity Chemistry immune synapse Cell Membrane T-cell receptor Multivesicular Bodies Protein kinase C δ Actins Cell biology Protein Kinase C-delta cell death RNA Interference lipids (amino acids peptides and proteins) lcsh:RC581-607 |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Frontiers in Immunology Biblos-e Archivo. Repositorio Institucional de la UAM Frontiers in Immunology, Vol 10 (2019) |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2019.00851 |
| Popis: | © 2019 Herranz, Aguilera, Dávila, Sánchez, Stancu, Gómez, Fernández-Moreno, de Martín, Quintanilla, Fernández, Rodríguez-Silvestre, Márquez-Expósito, Bello-Gamboa, Fraile-Ramos, Calvo and Izquierdo. Multivesicular bodies (MVB) are endocytic compartments that enclose intraluminal vesicles (ILVs) formed by inward budding from the limiting membrane of endosomes. In T lymphocytes, ILVs are secreted as Fas ligand-bearing, pro-apoptotic exosomes following T cell receptor (TCR)-induced fusion of MVB with the plasma membrane at the immune synapse (IS). In this study we show that protein kinase C δ (PKCδ), a novel PKC isotype activated by diacylglycerol (DAG), regulates TCR-controlled MVB polarization toward the IS and exosome secretion. Concomitantly, we demonstrate that PKCδ-interfered T lymphocytes are defective in activation-induced cell death. Using a DAG sensor based on the C1 DAG-binding domain of PKCδ and a GFP-PKCδ chimera, we reveal that T lymphocyte activation enhances DAG levels at the MVB endomembranes which mediates the association of PKCδ to MVB. Spatiotemporal reorganization of F-actin at the IS is inhibited in PKCδ-interfered T lymphocytes. Therefore, we propose PKCδ as a DAG effector that regulates the actin reorganization necessary for MVB traffic and exosome secretion. This work was supported by grants from the Spanish Ministerio de Economía y Competitividad (MINECO), Plan Nacional de Investigación Científica (SAF2016-77561-R to MI, which was in part granted with FEDER-EC- funding). This work was partially supported by grant BFU2012-35067 to AF-R |
| Databáze: | OpenAIRE |
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