Back to Search Start Over

Aminoacyl-tRNA Synthetase-Interacting Multifunctional Protein 1/p43 Controls Endoplasmic Reticulum Retention of Heat Shock Protein gp96

Authors :
Han, Jung Min
Park, Sang Gyu
Liu, Bei
Park, Bum-Joon
Kim, Jin Young
Jin, Cheng He
Song, Yeong Wook
Li, Zihai
Kim, Sunghoon
Source :
American Journal of Pathology; June 2007, Vol. 170 Issue: 6 p2042-2054, 13p
Publication Year :
2007

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.

Details

Language :
English
ISSN :
00029440
Volume :
170
Issue :
6
Database :
Supplemental Index
Journal :
American Journal of Pathology
Publication Type :
Periodical
Accession number :
ejs23568750
Full Text :
https://doi.org/10.2353/ajpath.2007.061266