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Published 5 January 2004. doi:10.1083/jcb.200306112
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 164, Number 1, 145-155
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Article

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

Alessandra Cambi1, Frank de Lange1, Noortje M. van Maarseveen4, Monique Nijhuis4, Ben Joosten1, Erik M.H.P. van Dijk5, Bärbel I. de Bakker5, Jack A.M. Fransen2, Petra H.M. Bovee-Geurts3, Frank N. van Leeuwen1, Niek F. Van Hulst5 and Carl G. Figdor1

1 Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
2 Department of Cell Biology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
3 Department of Medical Biochemistry, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
4 Department of Virology, University Medical Center Utrecht, 3508 GA Utrecht, Netherlands
5 Applied Optics Group, Department of Science and Technology, Molecular Engineering Sensors and Actuators Research Institute for Nanotechnology, University of Twente, 7500 AE Enschede, Netherlands

Address correspondence to Carl G. Figdor, Dept. of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, Netherlands. Tel.: 31-24-361-7600. Fax: 31-24-354-0339. email: c.figdor{at}ncmls.kun.nl

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.

Key Words: pathogen recognition receptor; lectin; electron microscopy; multiprotein assembly; lipid rafts


The online version of this article contains supplemental material.


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