PMID- 33425891
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210112
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 8
DP  - 2020
TI  - IRAP Endosomes Control Phagosomal Maturation in Dendritic Cells.
PG  - 585713
LID - 10.3389/fcell.2020.585713 [doi]
LID - 585713
AB  - Dendritic cells (DCs) contribute to the immune surveillance by sampling their 
      environment through phagocytosis and endocytosis. We have previously reported 
      that, rapidly following uptake of extracellular antigen into phagosomes or 
      endosomes in DCs, a specialized population of storage endosomes marked by Rab14 
      and insulin-regulated aminopeptidase (IRAP) is recruited to the nascent 
      antigen-containing compartment, thereby regulating its maturation and ultimately 
      antigen cross-presentation to CD8(+) T lymphocytes. Here, using IRAP(-/-) DCs, we 
      explored how IRAP modulates phagosome maturation dynamics and cross-presentation. 
      We find that in the absence of IRAP, phagosomes acquire more rapidly late 
      endosomal markers, are more degradative, and show increased microbicidal 
      activity. We also report evidence for a role of vesicle trafficking from the 
      endoplasmic reticulum (ER)-Golgi intermediate compartment to endosomes for the 
      formation or stability of the IRAP compartment. Moreover, we dissect the dual 
      role of IRAP as a trimming peptidase and a critical constituent of endosome 
      stability. Experiments using a protease-dead IRAP mutant and pharmacological IRAP 
      inhibition suggest that IRAP expression but not proteolytic activity is required 
      for the formation of storage endosomes and for DC-typical phagosome maturation, 
      whereas proteolysis is required for fully efficient cross-presentation. These 
      findings identify IRAP as a key factor in cross-presentation, trimming peptides 
      to fit the major histocompatibility complex class-I binding site while preventing 
      their destruction through premature phagosome maturation.
CI  - Copyright (c) 2020 Weimershaus, Mauvais, Evnouchidou, Lawand, Saveanu and van 
      Endert.
FAU - Weimershaus, Mirjana
AU  - Weimershaus M
AD  - Institut National de la Sante et de la Recherche Medicale, Unite 1151, Universite 
      de Paris, Centre National de la Recherche Scientifique, UMR 8253, Paris, France.
FAU - Mauvais, Francois-Xavier
AU  - Mauvais FX
AD  - Institut National de la Sante et de la Recherche Medicale, Unite 1151, Universite 
      de Paris, Centre National de la Recherche Scientifique, UMR 8253, Paris, France.
FAU - Evnouchidou, Irini
AU  - Evnouchidou I
AD  - Institut National de la Sante et de la Recherche Medicale, Unite 1151, Universite 
      de Paris, Centre National de la Recherche Scientifique, UMR 8253, Paris, France.
AD  - Inovarion, Paris, France.
FAU - Lawand, Myriam
AU  - Lawand M
AD  - Institut National de la Sante et de la Recherche Medicale, Unite 1151, Universite 
      de Paris, Centre National de la Recherche Scientifique, UMR 8253, Paris, France.
FAU - Saveanu, Loredana
AU  - Saveanu L
AD  - Institut National de la Sante et de la Recherche Medicale, Unite 1151, Universite 
      de Paris, Centre National de la Recherche Scientifique, UMR 8253, Paris, France.
FAU - van Endert, Peter
AU  - van Endert P
AD  - Institut National de la Sante et de la Recherche Medicale, Unite 1151, Universite 
      de Paris, Centre National de la Recherche Scientifique, UMR 8253, Paris, France.
LA  - eng
PT  - Journal Article
DEP - 20201211
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC7793786
OTO - NOTNLM
OT  - ERGIC
OT  - GLUT4-storage vesicle
OT  - aminopeptidase
OT  - cross-presentation
OT  - oxytocinase
OT  - phagosome maturation
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/01/12 06:00
MHDA- 2021/01/12 06:01
PMCR- 2020/01/01
CRDT- 2021/01/11 05:42
PHST- 2020/07/21 00:00 [received]
PHST- 2020/11/04 00:00 [accepted]
PHST- 2021/01/11 05:42 [entrez]
PHST- 2021/01/12 06:00 [pubmed]
PHST- 2021/01/12 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fcell.2020.585713 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2020 Dec 11;8:585713. doi: 10.3389/fcell.2020.585713. 
      eCollection 2020.