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Protein kinase C δ regulates the depletion of actin at the immunological synapse required for polarized exosome secretion by T cells

AuthorsHerranz, 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-Expósito, Laura; Bello Gamboa, Ana; Fraile-Ramos, Alberto; Calvo, Victor ; Izquierdo, Manuel
KeywordsT lymphocytes
Immune synapse
Protein kinase C δ
Multivesicular bodies
Cytotoxic activity
Cell death
Issue Date26-Apr-2019
PublisherFrontiers Media
CitationFrontiers in Immunology 10: 851 (2019)
AbstractMultivesicular 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.
Description© 2019 Herranz, Aguilera, Dávila, Sánchez, Stancu, Gómez, Fernández-Moreno, de Martín, Quintanilla, Fernández, Rodríguez-Silvestre, Márquez-Expósito, Bello-Gamboa, Fraile-Ramos, Calvo and Izquierdo.
Publisher version (URL)http://dx.doi.org/10.3389/fimmu.2019.00851
Appears in Collections:(IIBM) Artículos
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