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
PY - 2004
Y1 - 2004
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.
U2 - 10.1083/jcb.200306112
DO - 10.1083/jcb.200306112
M3 - Article
SN - 0021-9525
VL - 164
SP - 145
EP - 155
JO - Journal of cell biology
JF - Journal of cell biology
IS - 1
ER -
