Published online 23 February 2004. doi:10.1083/jcb.200312073
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 164, Number 5, 667-675
Dendritic cell aggresome-like induced structures are dedicated areas for ubiquitination and storage of newly synthesized defective proteins
Hugues Lelouard,
Vincent Ferrand,
Didier Marguet,
Jacek Bania,
Voahirana Camosseto,
Alexandre David,
Evelina Gatti, and
Philippe Pierre
Centre d'Immunologie de Marseille-Luminy, CNRS-INSERM-Université de la Méditerranée, Campus de Luminy, 13288 Marseille Cedex 09, France
Address correspondence to Philippe Pierre, Centre d'Immunologie de Marseille-Luminy, CNRS-INSERM-Université de la Méditerranée, Parc Scientifique de Luminy case 906, 13288 Marseille Cedex 09, France. Tel.: 33-4-91-26-94-79. Fax: 33-4-91-26-94-30. email: pierre{at}ciml.univ-mrs.fr
In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control antigen processing and presentation. One of these mechanisms is the sorting of polyubiquitinated proteins in large cytosolic aggregates called dendritic cell aggresome-like induced structures (DALIS). DALIS formation and maintenance are tightly linked to protein synthesis. Here, we took advantage of an antibody recognizing the antibiotic puromycin to follow the fate of improperly translated proteins, also called defective ribosomal products (DRiPs). We demonstrate that DRiPs are rapidly stored and protected from degradation in DALIS. In addition, we show that DALIS contain the ubiquitin-activating enzyme E1, the ubiquitin-conjugating enzyme E225K, and the COOH terminus of Hsp70-interacting protein ubiquitin ligase. The accumulation of these enzymes in the central area of DALIS defines specific functional sites where initial DRiP incorporation and ubiquitination occur. Therefore, DCs are able to regulate DRiP degradation in response to pathogen-associated motifs, a capacity likely to be important for their immune functions.
Key Words: DRiPs; DALIS; puromycin; dendritic cells; antigen processing
The online version of this article includes supplemental material.
Abbreviations used in this paper: CHIP, COOH terminus of Hsp70-interacting protein; DALIS, dendritic cell aggresome-like induced structures; DC, dendritic cell; DIC, differential interference contrast; DRiP, defective ribosomal product; LPS, lipopolysaccharide.
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