The truncated cytoplasmic tail of HLA-G serves a quality-control function in post-ER compartments.
In contrast to the current model of MHC class I trafficking, which predicts that once a MHC class I molecule leaves the ER, it moves to the cell surface by bulk flow, we show that HLA-G that is loaded with suboptimal peptides is retrieved from post-ER compartments to the ER. Loading of HLA-G with high-affinity peptides abrogates this retrieval due to the lack of binding affinity to coatomer. Moreover, the loss of the endocytosis motif in the truncated cytoplasmic tail results in the prolonged half-life of HLA-G on the cell surface. Our findings reveal that surface expression of HLA-G can be further regulated in post-ER compartments and that the truncated cytoplasmic tail plays a critical role in such quality-control mechanisms.
Park
B
B
Graduate School of Biotechnology, Korea University, Seoul 136-701, South Korea.
Lee
S
S
Kim
E
E
Chang
S
S
Jin
M
M
Ahn
K
K
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism*; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006680:HLA Antigens / Q000378:metabolism*; D059951:HLA-G Antigens; D006207:Half-Life; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008239:Lysine; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D021381:Protein Transport; D014407:Tumor Cells, Cultured
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D010455:Peptides; D008239:Lysine