TY - JOUR
T1 - Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells
AU - Cambi, Alessandra
AU - de Lange, Frank
AU - van Maarseveen, Noortje M
AU - Nijhuis, Monique
AU - Joosten, Ben
AU - van Dijk, Erik M H P
AU - de Bakker, Bärbel I
AU - Fransen, Jack A M
AU - Bovee-Geurts, Petra H M
AU - van Leeuwen, Frank N
AU - Van Hulst, Niek F
AU - Figdor, Carl G
PY - 2004/1/5
Y1 - 2004/1/5
N2 - 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.
AB - 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.
KW - Cell Adhesion Molecules/immunology
KW - Cell Membrane/metabolism
KW - Cells, Cultured
KW - Dendritic Cells/metabolism
KW - Endocytosis/physiology
KW - HIV Infections/immunology
KW - HIV-1/pathogenicity
KW - Humans
KW - Immunohistochemistry
KW - Lectins, C-Type/immunology
KW - Membrane Microdomains/metabolism
KW - Microscopy, Electron
KW - Monocytes/metabolism
KW - Protein Structure, Tertiary/physiology
KW - RNA Virus Infections/immunology
KW - Receptors, Cell Surface/immunology
KW - Receptors, Virus/immunology
UR - https://www.scopus.com/pages/publications/0347122962
U2 - 10.1083/jcb.200306112
DO - 10.1083/jcb.200306112
M3 - Article
C2 - 14709546
SN - 0021-9525
VL - 164
SP - 145
EP - 155
JO - The Journal of Cell Biology
JF - The Journal of Cell Biology
IS - 1
ER -