title: CD83 and GRASP55 interact in human dendritic cells.
abstract: CD83 is one of the best known surface markers for mature human dendritic cells (DCs). The full-length 45 kDa type-I membrane-bound form (mbCD83) is strongly glycosylated upon DCs maturation. As co-stimulatory properties of CD83 are attributed to mbCD83 surface expression is required for efficient T-cell stimulation by mature DCs. By yeast two-hybrid screening, we were able to identify GRASP55 as interaction partner of CD83. DCs maturation induces endogenous CD83 protein expression with simultaneous regulation of CD83 glycosylation, interaction and co-localization with GRASP55 and CD83 surface exposure. GRASP55 is especially known for its role in maintaining Golgi architecture, but also plays a role in Golgi transport of specific cargo proteins bearing a C-terminal valine residue. Here we additionally demonstrate that binding of CD83 and GRASP55 rely on the C-terminal TELV-motif of CD83. Mutation of this TELV-motif not only disrupted binding to GRASP55, but also altered the glycosylation pattern of CD83 and reduced its membrane expression. Here we show for the first time that GRASP55 interacts with CD83 shortly after induction of DC maturation and that this interaction plays a role in CD83 glycosylation as well as in surface expression of CD83 on DCs.
authors.affiliation: Department of Immune Modulation, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Marcello F
authors.initials: MF
authors.lastname: Stein
authors.affiliation: Department of Immune Modulation, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Blume
authors.affiliation: Department of Immune Modulation, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Christiane S
authors.initials: CS
authors.lastname: Heilingloh
authors.affiliation: Department of Immune Modulation, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Mirko
authors.initials: M
authors.lastname: Kummer
authors.affiliation: Institute of Virology, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Biesinger
authors.affiliation: Department of Biochemistry, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sticht
authors.affiliation: Department of Immune Modulation, Universitätsklinikum Erlangen, Erlangen, Germany. Electronic address: alexander.steinkasserer@uk-erlangen.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Steinkasserer
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D006031:Glycosylation; D000077614:Golgi Matrix Proteins; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D020798:Two-Hybrid System Techniques; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D000077614:Golgi Matrix Proteins; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D000097802:CD83 Antigen; C122048:GORASP2 protein, human
keywords: CD83; Dendritic cells; GRASP55; Golgi