title: VXFD in the cytoplasmic domain of macrophage scavenger receptors mediates their efficient internalization and cell-surface expression.
abstract: We determined the endocytosis motif sequence of macrophage scavenger receptors by measuring the internalization of the ligand-bound cell-surface scavenger receptors at the early stage. Mutation experiments have indicated that the 28 amino acids at the N-terminal cytoplasmic domain are important for both efficient internalization and cell-surface expression of the receptor. The substitution of alanine for Val21, Phe23 or Asp24 reduced both the efficiency of internalization and the cell-surface expression of the receptors; in addition, that for Val28 reduced only the internalization efficiency and that for Lys22 reduced only the cell-surface expression of the receptors. Western blot experiments showed that the total levels of expression of the mutant receptors in the cells were approximately the same and all the mutants were identified in the membrane fraction. This suggests that the Val21, Lys22, Phe23 and Asp24 mutants are localized in membranes other than the cell-surface membrane by missorting. All our results indicate that VXFD is the motif sequence essential for not only the coated-pit-mediated endocytosis of macrophage scavenger receptors but also for the trafficking of the receptors to the cell surface.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Morimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Wada
authors.forename: J
authors.initials: J
authors.lastname: Hinagata
authors.forename: T
authors.initials: T
authors.lastname: Imanishi
authors.forename: T
authors.initials: T
authors.lastname: Kodama
authors.forename: T
authors.initials: T
authors.lastname: Doi
mesh_terms: D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D004705:Endocytosis / Q000502:physiology*; D009154:Mutation; D017433:Protein Structure, Secondary; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051116:Receptors, Scavenger
chemical_list: D011971:Receptors, Immunologic; D051116:Receptors, Scavenger