Academic Journal
Protein kinase C δ regulates the depletion of actin at the immunological synapse required for polarized exosome secretion by T cells
العنوان: | Protein kinase C δ regulates the depletion of actin at the immunological synapse required for polarized exosome secretion by T cells |
---|---|
المؤلفون: | 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, Víctor, Izquierdo, Manuel |
المساهمون: | UAM. Departamento de Bioquímica |
بيانات النشر: | Frontiers Media |
سنة النشر: | 2020 |
المجموعة: | Universidad Autónoma de Madrid (UAM): Biblos-e Archivo |
مصطلحات موضوعية: | T lymphocytes, immune synapse, protein kinase C δ, multivesicular bodies, exosomes, cytotoxic activity, cell death, Medicina |
الوصف: | 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 |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 1664-3224 |
Relation: | Frontiers in Immunology; https://doi.org/10.3389/fimmu.2019.00851; Gobierno de España. SAF2016-77561-R; Gobierno de España. BFU2012-35067; Front. Immunol. 10 (2019): 851; http://hdl.handle.net/10486/690759; 851-1; 851-19; 10 |
DOI: | 10.3389/fimmu.2019.00851 |
الاتاحة: | http://hdl.handle.net/10486/690759 https://doi.org/10.3389/fimmu.2019.00851 |
Rights: | Copyright © 2019 Herranz, Aguilera, Dávila, Sánchez, Stancu, Gómez, Fernández- Moreno, de Martín, Quintanilla, Fernández, Rodríguez-Silvestre, Márquez- Expósito, Bello-Gamboa, Fraile-Ramos, Calvo and Izquierdo ; Reconocimiento ; openAccess |
رقم الانضمام: | edsbas.DBD404F9 |
قاعدة البيانات: | BASE |
تدمد: | 16643224 |
---|---|
DOI: | 10.3389/fimmu.2019.00851 |