Dendritic cell aggresome-like induced structures are dedicated areas for ubiquitination and storage of newly synthesized defective proteins.
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.
Centre d'Immunologie de Marseille-Luminy, CNRS-INSERM-Université de la Méditerranée, Parc Scientifique de Luminy case 906, 13288 Marseille Cedex 09, France.
Hugues
H
Lelouard
Vincent
V
Ferrand
Didier
D
Marguet
Jacek
J
Bania
Voahirana
V
Camosseto
Alexandre
A
David
Evelina
E
Gatti
Philippe
P
Pierre
D000818:Animals; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000502:physiology*; D036681:Fluorescence Recovery After Photobleaching; D002479:Inclusion Bodies / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D011691:Puromycin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D009097:Multienzyme Complexes; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D011993:Recombinant Fusion Proteins; D025801:Ubiquitin; D011691:Puromycin; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D044764:Ubiquitin-Activating Enzymes