title: Regulation of MHC class I transport by the molecular chaperone, calnexin (p88, IP90).
abstract: Assembled class I histocompatibility molecules, consisting of heavy chain, beta 2-microglobulin, and peptide ligand, are transported rapidly to the cell surface. In contrast, the intracellular transport of free heavy chains or peptide-deficient heavy chain-beta 2-microglobulin heterodimers is impaired. A 90-kilodalton membrane-bound chaperone of the endoplasmic reticulum (ER), termed calnexin, associates quantitatively with newly synthesized class I heavy chains, but the functions of calnexin in this interaction are unknown. Class I subunits were expressed alone or in combination with calnexin in Drosophila melanogaster cells. Calnexin retarded the intracellular transport of both peptide-deficient heavy chain-beta 2-microglobulin heterodimers and free heavy chains. Calnexin also impeded the rapid intracellular degradation of free heavy chains. The ability of calnexin to protect and retain class I assembly intermediates is likely to contribute to the efficient intracellular formation of class I-peptide complexes.
authors.affiliation: Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
authors.forename: M R
authors.initials: MR
authors.lastname: Jackson
authors.forename: M F
authors.initials: MF
authors.lastname: Cohen-Doyle
authors.forename: P A
authors.initials: PA
authors.lastname: Peterson
authors.forename: D B
authors.initials: DB
authors.lastname: Williams
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D037281:Calnexin; D002460:Cell Line; D004331:Drosophila melanogaster; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D013696:Temperature; D014162:Transfection; D001613:beta 2-Microglobulin / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D001613:beta 2-Microglobulin; D037281:Calnexin