title: Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells.
abstract: The C-type lectin dendritic cell (DC)-specific intercellular adhesion molecule grabbing non-integrin (DC-SIGN; CD209) facilitates binding and internalization of several viruses, including HIV-1, on DCs, but the underlying mechanism for being such an efficient phagocytic pathogen-recognition receptor is poorly understood. By high resolution electron microscopy, we demonstrate a direct relation between DC-SIGN function as viral receptor and its microlocalization on the plasma membrane. During development of human monocyte-derived DCs, DC-SIGN becomes organized in well-defined microdomains, with an average diameter of 200 nm. Biochemical experiments and confocal microscopy indicate that DC-SIGN microdomains reside within lipid rafts. Finally, we show that the organization of DC-SIGN in microdomains on the plasma membrane is important for binding and internalization of virus particles, suggesting that these multimolecular assemblies of DC-SIGN act as a docking site for pathogens like HIV-1 to invade the host.
authors.affiliation: Dept. of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, Netherlands.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cambi
authors.forename: Frank
authors.initials: F
authors.lastname: de Lange
authors.forename: Noortje M
authors.initials: NM
authors.lastname: van Maarseveen
authors.forename: Monique
authors.initials: M
authors.lastname: Nijhuis
authors.forename: Ben
authors.initials: B
authors.lastname: Joosten
authors.forename: Erik M H P
authors.initials: EM
authors.lastname: van Dijk
authors.forename: Bärbel I
authors.initials: BI
authors.lastname: de Bakker
authors.forename: Jack A M
authors.initials: JA
authors.lastname: Fransen
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Bovee-Geurts
authors.forename: Frank N
authors.initials: FN
authors.lastname: van Leeuwen
authors.forename: Niek F
authors.initials: NF
authors.lastname: Van Hulst
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
mesh_terms: D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology; D004705:Endocytosis / Q000502:physiology; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D021962:Membrane Microdomains / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D009000:Monocytes / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D017434:Protein Structure, Tertiary / Q000502:physiology; D012327:RNA Virus Infections / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D011991:Receptors, Virus / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin