Article abstract
Nature Cell Biology 9, 367 - 378 (2007)
Published online: 11 March 2007 | doi:10.1038/ncb1552
Rab27a regulates phagosomal pH and NADPH oxidase recruitment to dendritic cell phagosomes
Carolina Jancic1,6, Ariel Savina1,6, Christina Wasmeier2, Tanya Tolmachova2, Jamel El-Benna3, Pham My-Chan Dang3, Steve Pascolo4, Maire-Anne Gougerot-Pocidalo3, Graça Raposo5, Miguel C. Seabra2 & Sebastian Amigorena1
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.
- Institut Curie, INSERM U653, Immunité et Cancer, 26 rue d'Ulm, 75248 Paris, Cedex 05, France.
- Molecular and Cellular Medicine, NHLI, Imperial College London, Exhibition Rd, London SW7 2AZ, UK.
- INSERM U773,Centre de Recherche Biomedicale Bichat Beaujon CRB3; Université Paris 7 Denis Diderot, site Bichat, UMRS 773, Paris, F-75018, France.
- Department of Immunology University of Tuebingen, Auf der Morgenstelle 15, 72076 Tuebingen, Germany.
- Institut Curie, CNRS-UMR144, Structure et Compartiments Membranaires, 26 rue d'Ulm, 75248 Paris, Cedex 05, France.
- These authors contributed equally to this work.
Correspondence to: Sebastian Amigorena1 e-mail: sebastian.amigorena@curie.fr
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
New ways to arrest phagosome maturationNature Cell Biology News and Views (01 Apr 2007)
Cell biology The extraordinary phagosomeNature News and Views (18 Jul 2002)
See all 9 matches for News And ViewsRESEARCH
TI-VAMP/VAMP7 is required for optimal phagocytosis of opsonised particles in macrophagesThe EMBO Journal Article (27 Oct 2004)
ER?phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cellsNature Letters to Editor (25 Sep 2003)
See all 53 matches for Research