Bap31 enhances the endoplasmic reticulum export and quality control of human class I MHC molecules

被引:54
作者
Ladasky, John J.
Boyle, Sarah
Seth, Malini
Li, Hewang
Pentcheva, Tsvetelina
Abe, Fumiyoshi
Steinberg, Steven J.
Edidin, Michael
机构
[1] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA
[2] Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Baltimore, MD 21205 USA
关键词
D O I
10.4049/jimmunol.177.9.6172
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The assembly of class I MHC molecules and their export from the endoplasmic reticulum (ER) is governed by chaperones and accessory proteins. We present evidence that the putative cargo receptor protein Bap31 participates in the transport and the quality control of human class I molecules. Transfection of the human adenocarcinoma cell line HeLa with yellow fluorescent protein-Bap31 chimeras increased surface levels of class I in a dose-dependent manner, by as much as 3.7-fold. The increase in surface class I resulted from an increase in the rate of export of newly synthesized class I molecules to the cell surface and from an increase in the stability of the exported molecules. We propose that Bap31 performs quality control on class I molecules in two distinct phases: first, by exporting peptide-loaded class I molecules to the ER/Golgi intermediate compartment, and second, by retrieving class I molecules that have lost peptides in the acidic post-ER environment. This function of Bap31 is conditional or redundant, because we find that Bap31 deficiency does not reduce surface class I levels. Overexpression of the Bap31 homolog, Bap29, decreases surface class levels in HeLa, indicating that it does not substitute for Bap31.
引用
收藏
页码:6172 / 6181
页数:10
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