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Aminoacyl-tRNA synthetase-interacting multifunctional protein 1/p43 controls endoplasmic reticulum retention of heat shock protein gp96: its pathological implications in lupus-like autoimmune diseases
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- Authors
- Issue Date
- 2007-05-26
- Citation
- Am J Pathol. 2007 Jun;170(6):2042-54.
- Keywords
- Animals ; Autoimmune Diseases/*immunology ; Cells, Cultured ; Cytokines/genetics/*metabolism ; Dimerization ; Endoplasmic Reticulum/*metabolism ; Heat-Shock Proteins/genetics/*metabolism ; Lupus Erythematosus, Systemic/*immunology ; Membrane Glycoproteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Phenotype ; Receptors, Peptide/genetics/metabolism ; Recombinant Fusion Proteins/genetics/metabolism ; Spleen/cytology
- Abstract
- Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1; previously known as p43) is a multifunctional protein that was initially found in multitRNA synthetase complex. In the present study, screening of the AIMP1-binding proteins revealed that AIMP1 can form a molecular complex with heat shock protein gp96. AIMP1 enhances gp96 dimerization and the interaction between gp96 and KDEL receptor-1 (KDELR-1), which mediates the retrieval of KDEL-containing proteins from Golgi to the endoplasmic reticulum (ER). The interaction between gp96 and KDELR-1 was reduced in AIMP1-deficient cells, and this disturbed ER retention of gp96 and increased its cell surface localization. Moreover, this localization of gp96 at the cell surface was suppressed by its interaction with AIMP1 and enhanced by the depletion of endogenous AIMP1. In addition, AIMP1-deficient mice showed dendritic cell activation attributable to increased gp96 surface presentation and lupus-like autoimmune phenotypes. These results suggest that AIMP1 acts as a regulator of the ER retention of gp96 and provide a new perspective of the regulatory mechanism underlying immune stimulation by gp96.
- ISSN
- 0002-9440 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17525271
https://hdl.handle.net/10371/22542
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