Dendritic cell aggresome-like induced structures are dedicated areas for ubiquitination and storage of newly synthesized defective proteins

被引:123
作者
Lelouard, H [1 ]
Ferrand, V [1 ]
Marguet, D [1 ]
Bania, J [1 ]
Camosseto, V [1 ]
David, A [1 ]
Gatti, E [1 ]
Pierre, P [1 ]
机构
[1] Univ Mediterranee, Ctr Immunol Marseille Luminy, CNRS, INSERM, F-13288 Marseille 09, France
关键词
DRiPs; DALIS; puromycin; dendritic cells; antigen processing;
D O I
10.1083/jcb.200312073
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 El, the ubiquitin-conjugating enzyme E2(25K), 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.
引用
收藏
页码:667 / 675
页数:9
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