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...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/690759
Acceso en línea:http://hdl.handle.net/10486/690759
https://dx.doi.org/10.3389/fimmu.2019.00851
Access Level:acceso abierto
Palabra clave:T lymphocytes
immune synapse
protein kinase C δ
multivesicular bodies
exosomes
cytotoxic activity
cell death
Medicina
Descripción
Sumario: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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