Selective export of HLA-F by its cytoplasmic tail.
MHC class I molecules exit the endoplasmic reticulum (ER) by an unknown mechanism. Although a selective export mechanism has been proposed for the anterograde transport of class I, a motif responsible for export has never been identified. Although classical class I molecules lacking their cytoplasmic tail are expressed on the cell surface, we found that HLA-F was entirely dependent on its cytoplasmic tail for export from the ER. Two known export motifs were recognizable in HLA-F. A C-terminal valine residue functioned in ER export and interacted with coat complex (COP)II, while an RxR motif also played an important role in anterograde transport and bound to 14-3-3 proteins. This divergent trafficking of HLA-F implicates an alternative function for HLA-F, independent of loading with peptides in the ER.
Boyle
Louise H
LH
Department of Pathology, University of Cambridge, Cambridge, United Kingdom. lhb22@cam.ac.uk
Gillingham
Alison K
AK
Munro
Sean
S
Trowsdale
John
J
D048948:14-3-3 Proteins / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry / Q000378:metabolism; D022181:COP-Coated Vesicles / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015234:HLA-A Antigens / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D014633:Valine / Q000737:chemistry / Q000235:genetics
D048948:14-3-3 Proteins; D006680:HLA Antigens; D015234:HLA-A Antigens; C062341:HLA-F antigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D001120:Arginine; D014633:Valine