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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
|---|---|
| Format: | Article |
| Publication date: | 2019 |
| Country: | España |
| Institution: | Universidad Autónoma de Madrid |
| Repository: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Language: | English |
| OAI Identifier: | oai:repositorio.uam.es:10486/690759 |
| Online Access: | http://hdl.handle.net/10486/690759 https://dx.doi.org/10.3389/fimmu.2019.00851 |
| Access Level: | Open access |
| Keyword: | T lymphocytes immune synapse protein kinase C δ multivesicular bodies exosomes cytotoxic activity cell death Medicina |
| Summary: | 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. |
|---|