title: Accurate intracellular localization of HLA-DM requires correct spacing of a cytoplasmic YTPL targeting motif relative to the transmembrane domain.
abstract: HLA-DM is an MHC class II-related heterodimer that is targeted to lysosomal compartments by a tyrosine-based signal YTPL, present in the cytoplasmic tail of the beta chain. Similar signals in other proteins control transport to different intracellular locations and can be recognized at several sorting sites within the cell including the trans-Golgi network, the plasma membrane and the early or sorting endosome. Therefore, in addition to recognizing the basic tyrosine motif, the sorting machinery must be sensitive to additional features associated with these elements. Here we show that efficient trafficking of HLA-DM to lysosomal compartments is dependent upon the proximity of its tyrosine motif to the transmembrane domain. Constructs in which the spacing is altered are rapidly internalized but are expressed at the cell surface. We conclude that the spacing of the HLA-DMB-encoded tyrosine motif relative to the transmembrane domain is an important feature controlling DM sorting in endosomes.
authors.affiliation: Department of Nephrology Guy's, King's and St Thomas' School of Medicine, London, GB.
authors.forename: P K
authors.initials: PK
authors.lastname: Potter
authors.forename: J
authors.initials: J
authors.lastname: Copier
authors.forename: S H
authors.initials: SH
authors.lastname: Sacks
authors.forename: J
authors.initials: J
authors.lastname: Calafat
authors.forename: H
authors.initials: H
authors.lastname: Janssen
authors.forename: J J
authors.initials: JJ
authors.lastname: Neefjes
authors.forename: A P
authors.initials: AP
authors.lastname: Kelly
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D001692:Biological Transport; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II; D006801:Humans; D008969:Molecular Sequence Data; D014162:Transfection
chemical_list: C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II