Rab27a regulates phagosomal pH and NADPH oxidase recruitment to dendritic cell phagosomes.
To prevent excessive degradation of internalized antigens, which could destroy the peptides recognized by T lymphocytes, dendritic cells have developed several strategies that limit proteolytic activity in phagosomes. The recruitment of the NADPH oxidase NOX2 prevents acidification of phagosomes, limiting antigen degradation. Here, we show that dendritic cells derived from Rab27a-deficient ashen mice show increased phagosome acidification and antigen degradation, causing a defect in antigen cross-presentation. Enhanced acidification results from a delay in the recruitment to phagosomes of a subset of lysosome-related organelles containing the membrane subunits of NOX2. The Rab27a-dependent recruitment of these "inhibitory lysosome-related organelles" to phagosomes continuously limits acidification and degradation of ingested particles in dendritic cells, thus promoting antigen cross-presentation.
Jancic
Carolina
C
Institut Curie, INSERM U653, Immunité et Cancer, 26 rue d'Ulm, 75248 Paris, Cedex 05, France.
Savina
Ariel
A
Wasmeier
Christina
C
Tolmachova
Tanya
T
El-Benna
Jamel
J
Dang
Pham My-Chan
PM
Pascolo
Steve
S
Gougerot-Pocidalo
Maire-Anne
MA
Raposo
Graça
G
Seabra
Miguel C
MC
Amigorena
Sebastian
S
D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D019255:NADPH Oxidases / Q000378:metabolism*; D010047:Ovalbumin / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000075745:rab27 GTP-Binding Proteins
D052118:Lysosomal-Associated Membrane Protein 1; D017382:Reactive Oxygen Species; D000075745:rab27 GTP-Binding Proteins; D049452:Green Fluorescent Proteins; D010047:Ovalbumin; D019255:NADPH Oxidases; C512962:Rab27a protein, mouse; D020691:rab GTP-Binding Proteins