Transient aggregation of ubiquitinated proteins during dendritic cell maturation.
Dendritic cells (DCs) are antigen-presenting cells with the unique capacity to initiate primary immune responses. Dendritic cells have a remarkable pattern of differentiation (maturation) that exhibits highly specific mechanisms to control antigen presentation restricted by major histocompatibility complex (MHC). MHC class I molecules present to CD8(+) cytotoxic T cells peptides that are derived mostly from cytosolic proteins, which are ubiquitinated and then degraded by the proteasome. Here we show that on inflammatory stimulation, DCs accumulate newly synthesized ubiquitinated proteins in large cytosolic structures. These structures are similar to, but distinct from, aggresomes and inclusion bodies observed in many amyloid diseases. Notably, these dendritic cell aggresome-like induced structures (DALIS) are transient, require continuous protein synthesis and do not affect the ubiquitin-proteasome pathway. Our observations suggest the existence of an organized prioritization of protein degradation in stimulated DCs, which is probably important for regulating MHC class I presentation during maturation.
Lelouard
Hugues
H
Centre d'Immunolgie de Marseille-Luminy, CNRS-INSERM-Université Med., Marseille, France.
Gatti
Evelina
E
Cappello
Fanny
F
Gresser
Olivia
O
Camosseto
Voahirana
V
Pierre
Philippe
P
D000818:Animals; D017951:Antigen Presentation; D002172:Canavanine / Q000494:pharmacology; D020134:Catalytic Domain; D002454:Cell Differentiation / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding / Q000187:drug effects; D014176:Protein Biosynthesis; D011489:Protein Denaturation; D021122:Protein Subunits; D021381:Protein Transport / Q000187:drug effects; D025801:Ubiquitin / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I; D008070:Lipopolysaccharides; D009097:Multienzyme Complexes; D009842:Oligopeptides; D021122:Protein Subunits; D025801:Ubiquitin; D002172:Canavanine; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D015739:Nocodazole; C078846:epoxomicin