Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells.
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.
Cambi
Alessandra
A
Dept. of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, Netherlands.
de Lange
Frank
F
van Maarseveen
Noortje M
NM
Nijhuis
Monique
M
Joosten
Ben
B
van Dijk
Erik M H P
EM
de Bakker
Bärbel I
BI
Fransen
Jack A M
JA
Bovee-Geurts
Petra H M
PH
van Leeuwen
Frank N
FN
Van Hulst
Niek F
NF
Figdor
Carl G
CG
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
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin