Protein Kinase C δ Regulates the Depletion of Actin at the Immunological Synapse Required for Polarized Exosome Secretion by T Cells
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 w...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00851/full |
| _version_ | 1811268681793011712 |
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| author | Gonzalo Herranz Pablo Aguilera Sergio Dávila Alicia Sánchez Bianca Stancu Jesús Gómez David Fernández-Moreno Raúl de Martín Mario Quintanilla Teresa Fernández Pablo Rodríguez-Silvestre Laura Márquez-Expósito Ana Bello-Gamboa Alberto Fraile-Ramos Víctor Calvo Manuel Izquierdo |
| author_facet | Gonzalo Herranz Pablo Aguilera Sergio Dávila Alicia Sánchez Bianca Stancu Jesús Gómez David Fernández-Moreno Raúl de Martín Mario Quintanilla Teresa Fernández Pablo Rodríguez-Silvestre Laura Márquez-Expósito Ana Bello-Gamboa Alberto Fraile-Ramos Víctor Calvo Manuel Izquierdo |
| author_sort | Gonzalo Herranz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T21:27:15Z |
| format | Article |
| id | doaj.art-dfd47d83a52f49deab2729eb9e5caebe |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T21:27:15Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-dfd47d83a52f49deab2729eb9e5caebe2022-12-22T03:16:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-04-011010.3389/fimmu.2019.00851430158Protein Kinase C δ Regulates the Depletion of Actin at the Immunological Synapse Required for Polarized Exosome Secretion by T CellsGonzalo Herranz0Pablo Aguilera1Sergio Dávila2Alicia Sánchez3Bianca Stancu4Jesús Gómez5David Fernández-Moreno6Raúl de Martín7Mario Quintanilla8Teresa Fernández9Pablo Rodríguez-Silvestre10Laura Márquez-Expósito11Ana Bello-Gamboa12Alberto Fraile-Ramos13Víctor Calvo14Manuel Izquierdo15Departamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainDepartamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainDepartamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainDepartamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainDepartamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainDepartamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainDepartamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainDepartamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainDepartamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainDepartamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainDepartamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainDepartamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainDepartamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainDepartamento de Biología Celular, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, SpainDepartamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainDepartamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Madrid, SpainMultivesicular 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.00851/fullT lymphocytesimmune synapseprotein kinase C δmultivesicular bodiesexosomescytotoxic activity |
| spellingShingle | Gonzalo Herranz Pablo Aguilera Sergio Dávila Alicia Sánchez Bianca Stancu Jesús Gómez David Fernández-Moreno Raúl de Martín Mario Quintanilla Teresa Fernández Pablo Rodríguez-Silvestre Laura Márquez-Expósito Ana Bello-Gamboa Alberto Fraile-Ramos Víctor Calvo Manuel Izquierdo Protein Kinase C δ Regulates the Depletion of Actin at the Immunological Synapse Required for Polarized Exosome Secretion by T Cells Frontiers in Immunology T lymphocytes immune synapse protein kinase C δ multivesicular bodies exosomes cytotoxic activity |
| title | Protein Kinase C δ Regulates the Depletion of Actin at the Immunological Synapse Required for Polarized Exosome Secretion by T Cells |
| title_full | Protein Kinase C δ Regulates the Depletion of Actin at the Immunological Synapse Required for Polarized Exosome Secretion by T Cells |
| title_fullStr | Protein Kinase C δ Regulates the Depletion of Actin at the Immunological Synapse Required for Polarized Exosome Secretion by T Cells |
| title_full_unstemmed | Protein Kinase C δ Regulates the Depletion of Actin at the Immunological Synapse Required for Polarized Exosome Secretion by T Cells |
| title_short | Protein Kinase C δ Regulates the Depletion of Actin at the Immunological Synapse Required for Polarized Exosome Secretion by T Cells |
| title_sort | protein kinase c δ regulates the depletion of actin at the immunological synapse required for polarized exosome secretion by t cells |
| topic | T lymphocytes immune synapse protein kinase C δ multivesicular bodies exosomes cytotoxic activity |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00851/full |
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