Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells

Alessandra Cambi, Frank de Lange, Noortje M van Maarseveen, Monique Nijhuis, Ben Joosten, Erik M H P van Dijk, Bärbel I de Bakker, Jack A M Fransen, Petra H M Bovee-Geurts, Frank N van Leeuwen, Niek F Van Hulst, Carl G Figdor

Research output: Contribution to journalArticlepeer-review

199 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)145-55
Number of pages11
JournalThe Journal of Cell Biology
Issue number1
Publication statusPublished - 5 Jan 2004
Externally publishedYes


  • Cell Adhesion Molecules/immunology
  • Cell Membrane/metabolism
  • Cells, Cultured
  • Dendritic Cells/metabolism
  • Endocytosis/physiology
  • HIV Infections/immunology
  • HIV-1/pathogenicity
  • Humans
  • Immunohistochemistry
  • Lectins, C-Type/immunology
  • Membrane Microdomains/metabolism
  • Microscopy, Electron
  • Monocytes/metabolism
  • Protein Structure, Tertiary/physiology
  • RNA Virus Infections/immunology
  • Receptors, Cell Surface/immunology
  • Receptors, Virus/immunology


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