Bap31 enhances the endoplasmic reticulum export and quality control of human class I MHC molecules.
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.
Ladasky
John J
JJ
Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
Boyle
Sarah
S
Seth
Malini
M
Li
Hewang
H
Pentcheva
Tsvetelina
T
Abe
Fumiyoshi
F
Steinberg
Steven J
SJ
Edidin
Michael
M
D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics; D002462:Cell Membrane / Q000737:chemistry; D002467:Cell Nucleus / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics; D015533:Transcriptional Activation; D014162:Transfection
C486244:BCAP29 protein, human; C091247:BCAP31 protein, human; D001426:Bacterial Proteins; D015395:Histocompatibility Antigens Class I; D008164:Luminescent Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C054562:yellow fluorescent protein, Bacteria