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...
| Autores: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Tipo de documento: | Artigo |
| Data de publicação: | 2019 |
| País: | España |
| Recursos: | Universidad Autónoma de Madrid |
| Repositório: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | Inglês |
| OAI Identifier: | oai:repositorio.uam.es:10486/690759 |
| Acesso em linha: | http://hdl.handle.net/10486/690759 https://dx.doi.org/10.3389/fimmu.2019.00851 |
| Nível de acesso: | Acesso aberto |
| Palavra-chave: | T lymphocytes immune synapse protein kinase C δ multivesicular bodies exosomes cytotoxic activity cell death Medicina |
| Resumo: | 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. |
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