Protein kinase C δ regulates the depletion of actin at the immunological synapse required for polarized exosome secretion by T cells
Author
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
Entity
UAM. Departamento de BioquímicaPublisher
Frontiers MediaDate
2019-04-26Citation
10.3389/fimmu.2019.00851
Front. Immunol. 10 (2019): 851
ISSN
1664-3224DOI
10.3389/fimmu.2019.00851Funded by
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-RProject
Gobierno de España. SAF2016-77561-R; Gobierno de España. BFU2012-35067Editor's Version
https://doi.org/10.3389/fimmu.2019.00851Subjects
T lymphocytes; immune synapse; protein kinase C δ; multivesicular bodies; exosomes; cytotoxic activity; cell death; MedicinaRights
Copyright © 2019 Herranz, Aguilera, Dávila, Sánchez, Stancu, Gómez, Fernández- Moreno, de Martín, Quintanilla, Fernández, Rodríguez-Silvestre, Márquez- Expósito, Bello-Gamboa, Fraile-Ramos, Calvo and IzquierdoAbstract
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.
Files in this item
Google Scholar:Herranz, Gonzalo
-
Aguilera, Pablo
-
Dávila, Sergio
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Sánchez, Alicia
-
Stancu, Bianca
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Gómez, Jesús
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Fernández-Moreno, David
-
Martín, Raúl de
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Quintanilla, Mario
-
Fernández, Teresa
-
Rodríguez-Silvestre, Pablo
-
Márquez-Exposito, Laura
-
Bello-Gamboa, Ana
-
Fraile-Ramos, Alberto
-
Calvo López, Víctor
-
Izquierdo, Manuel
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