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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 2019 |
| Country: | España |
| Institution: | Universidad Autónoma de Madrid |
| Repository: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Language: | English |
| OAI Identifier: | oai:repositorio.uam.es:10486/690759 |
| Online Access: | http://hdl.handle.net/10486/690759 https://dx.doi.org/10.3389/fimmu.2019.00851 |
| Access Level: | Open access |
| Keyword: | T lymphocytes immune synapse protein kinase C δ multivesicular bodies exosomes cytotoxic activity cell death Medicina |
| _version_ | 1878738821102698496 |
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| author | Herranz, Gonzalo |
| author2 | Aguilera, Pablo Dávila, Sergio Sánchez, Alicia Stancu, Bianca Gómez, Jesús Fernández-Moreno, David Martín, Raúl de Quintanilla, Mario Fernández, Teresa Rodríguez-Silvestre, Pablo Márquez-Exposito, Laura Bello-Gamboa, Ana Fraile-Ramos, Alberto Calvo López, Víctor Izquierdo, Manuel |
| author2_role | author author author author author author author author author author author author author author author |
| author_browse | Aguilera, Pablo Bello-Gamboa, Ana Calvo López, Víctor Dávila, Sergio Fernández, Teresa Fernández-Moreno, David Fraile-Ramos, Alberto Gómez, Jesús Herranz, Gonzalo Izquierdo, Manuel Martín, Raúl de Márquez-Exposito, Laura Quintanilla, Mario Rodríguez-Silvestre, Pablo Stancu, Bianca Sánchez, Alicia |
| author_facet | Herranz, Gonzalo Aguilera, Pablo Dávila, Sergio Sánchez, Alicia Stancu, Bianca Gómez, Jesús Fernández-Moreno, David Martín, Raúl de Quintanilla, Mario Fernández, Teresa Rodríguez-Silvestre, Pablo Márquez-Exposito, Laura Bello-Gamboa, Ana Fraile-Ramos, Alberto Calvo López, Víctor Izquierdo, Manuel |
| author_role | author |
| collection | Biblos-e Archivo. Repositorio Institucional de la UAM |
| 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 (PKC δ ), a novel PKC isotype activated by diacylglycerol (DAG), regulates TCR-controlled MVB polarization toward the IS and exosome secretion. Concomitantly, we demonstrate that PKC δ -interfered T lymphocytes are defective in activation-induced cell death. Using a DAG sensor based on the C1 DAG-binding domain of PKC δ and a GFP-PKC δ chimera, we reveal that T lymphocyte activation enhances DAG levels at the MVB endomembranes which mediates the association of PKC δ to MVB. Spatiotemporal reorganization of F-actin at the IS is inhibited in PKC δ -interfered T lymphocytes. Therefore, we propose PKC δ as a DAG effector that regulates the actin reorganization necessary for MVB traffic and exosome secretion. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_b5c70d65f0df2fff2369dcb8b8b65257 |
| institution | Universidad Autónoma de Madrid |
| instname_str | Universidad Autónoma de Madrid |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:repositorio.uam.es:10486/690759 |
| publishDate | 2019 |
| publishDateSort | 2019 |
| publisher | Frontiers Media |
| publisherStr | Frontiers Media |
| reponame_str | Biblos-e Archivo. Repositorio Institucional de la UAM |
| spelling | Protein kinase C δ regulates the depletion of actin at the immunological synapse required for polarized exosome secretion by T cells Herranz, Gonzalo Aguilera, Pablo Dávila, Sergio Sánchez, Alicia Stancu, Bianca Gómez, Jesús Fernández-Moreno, David Martín, Raúl de Quintanilla, Mario Fernández, Teresa Rodríguez-Silvestre, Pablo Márquez-Exposito, Laura Bello-Gamboa, Ana Fraile-Ramos, Alberto Calvo López, Víctor Izquierdo, Manuel T lymphocytes immune synapse protein kinase C δ multivesicular bodies exosomes cytotoxic activity cell death Medicina 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 (PKC δ ), a novel PKC isotype activated by diacylglycerol (DAG), regulates TCR-controlled MVB polarization toward the IS and exosome secretion. Concomitantly, we demonstrate that PKC δ -interfered T lymphocytes are defective in activation-induced cell death. Using a DAG sensor based on the C1 DAG-binding domain of PKC δ and a GFP-PKC δ chimera, we reveal that T lymphocyte activation enhances DAG levels at the MVB endomembranes which mediates the association of PKC δ to MVB. Spatiotemporal reorganization of F-actin at the IS is inhibited in PKC δ -interfered T lymphocytes. Therefore, we propose PKC δ 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 Frontiers Media http://hdl.handle.net/10486/690759 https://dx.doi.org/10.3389/fimmu.2019.00851 |
| spellingShingle | Protein kinase C δ regulates the depletion of actin at the immunological synapse required for polarized exosome secretion by T cells Herranz, Gonzalo T lymphocytes immune synapse protein kinase C δ multivesicular bodies exosomes cytotoxic activity cell death Medicina |
| 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 cell death Medicina |
| topic_facet | T lymphocytes immune synapse protein kinase C δ multivesicular bodies exosomes cytotoxic activity cell death Medicina |
| url | http://hdl.handle.net/10486/690759 https://dx.doi.org/10.3389/fimmu.2019.00851 |