PMID- 31105694
OWN - NLM
STAT- MEDLINE
DCOM- 20200930
LR  - 20200930
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Protein Kinase C delta Regulates the Depletion of Actin at the Immunological Synapse 
      Required for Polarized Exosome Secretion by T Cells.
PG  - 851
LID - 10.3389/fimmu.2019.00851 [doi]
LID - 851
AB  - 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 delta (PKCdelta), a 
      novel PKC isotype activated by diacylglycerol (DAG), regulates TCR-controlled MVB 
      polarization toward the IS and exosome secretion. Concomitantly, we demonstrate 
      that PKCdelta-interfered T lymphocytes are defective in activation-induced cell 
      death. Using a DAG sensor based on the C1 DAG-binding domain of PKCdelta and a 
      GFP-PKCdelta chimera, we reveal that T lymphocyte activation enhances DAG levels at 
      the MVB endomembranes which mediates the association of PKCdelta to MVB. 
      Spatiotemporal reorganization of F-actin at the IS is inhibited in 
      PKCdelta-interfered T lymphocytes. Therefore, we propose PKCdelta as a DAG effector that 
      regulates the actin reorganization necessary for MVB traffic and exosome 
      secretion.
FAU - Herranz, Gonzalo
AU  - Herranz G
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
FAU - Aguilera, Pablo
AU  - Aguilera P
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
FAU - Davila, Sergio
AU  - Davila S
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
FAU - Sanchez, Alicia
AU  - Sanchez A
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
FAU - Stancu, Bianca
AU  - Stancu B
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
FAU - Gomez, Jesus
AU  - Gomez J
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
FAU - Fernandez-Moreno, David
AU  - Fernandez-Moreno D
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
FAU - de Martin, Raul
AU  - de Martin R
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
FAU - Quintanilla, Mario
AU  - Quintanilla M
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
FAU - Fernandez, Teresa
AU  - Fernandez T
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
FAU - Rodriguez-Silvestre, Pablo
AU  - Rodriguez-Silvestre P
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
FAU - Marquez-Exposito, Laura
AU  - Marquez-Exposito L
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
FAU - Bello-Gamboa, Ana
AU  - Bello-Gamboa A
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
FAU - Fraile-Ramos, Alberto
AU  - Fraile-Ramos A
AD  - Departamento de Biologia Celular, Facultad de Medicina, Universidad Complutense 
      de Madrid, Madrid, Spain.
FAU - Calvo, Victor
AU  - Calvo V
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
FAU - Izquierdo, Manuel
AU  - Izquierdo M
AD  - Departamento de Bioquimica, Instituto de Investigaciones Biomedicas Alberto Sols 
      CSIC-UAM, Madrid, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190426
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Actins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - EC 2.7.11.13 (Protein Kinase C-delta)
SB  - IM
MH  - Actins/*metabolism
MH  - Apoptosis/immunology
MH  - Cell Line, Tumor
MH  - Cell Membrane/metabolism
MH  - Exosomes/*metabolism
MH  - Humans
MH  - Jurkat Cells
MH  - Lymphocyte Activation/immunology
MH  - Multivesicular Bodies/*metabolism
MH  - Protein Kinase C-delta/genetics/*metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/genetics
MH  - Receptors, Antigen, T-Cell/metabolism
MH  - T-Lymphocytes/*immunology
PMC - PMC6499072
OTO - NOTNLM
OT  - T lymphocytes
OT  - cell death
OT  - cytotoxic activity
OT  - exosomes
OT  - immune synapse
OT  - multivesicular bodies
OT  - protein kinase C delta
EDAT- 2019/05/21 06:00
MHDA- 2020/10/02 06:00
PMCR- 2019/01/01
CRDT- 2019/05/21 06:00
PHST- 2018/10/11 00:00 [received]
PHST- 2019/04/02 00:00 [accepted]
PHST- 2019/05/21 06:00 [entrez]
PHST- 2019/05/21 06:00 [pubmed]
PHST- 2020/10/02 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.00851 [doi]
PST - epublish
SO  - Front Immunol. 2019 Apr 26;10:851. doi: 10.3389/fimmu.2019.00851. eCollection 
      2019.