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Nat Cell Biol. 2007 Apr;9(4):367-78. Epub 2007 Mar 11.

Rab27a regulates phagosomal pH and NADPH oxidase recruitment to dendritic cell phagosomes.

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1
Institut Curie, INSERM U653, Immunité et Cancer, 26 rue d'Ulm, 75248 Paris, Cedex 05, France.

Abstract

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.

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PMID:
17351642
DOI:
10.1038/ncb1552
[Indexed for MEDLINE]

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