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.
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5 January 2004
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January 05 2004
Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells
Alessandra Cambi,
Alessandra Cambi
1Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
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Frank de Lange,
Frank de Lange
1Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
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Noortje M. van Maarseveen,
Noortje M. van Maarseveen
4Department of Virology, University Medical Center Utrecht, 3508 GA Utrecht, Netherlands
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Monique Nijhuis,
Monique Nijhuis
4Department of Virology, University Medical Center Utrecht, 3508 GA Utrecht, Netherlands
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Ben Joosten,
Ben Joosten
1Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
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Erik M.H.P. van Dijk,
Erik M.H.P. van Dijk
5Applied Optics Group, Department of Science and Technology, Molecular Engineering Sensors and Actuators Research Institute for Nanotechnology, University of Twente, 7500 AE Enschede, Netherlands
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Bärbel I. de Bakker,
Bärbel I. de Bakker
5Applied Optics Group, Department of Science and Technology, Molecular Engineering Sensors and Actuators Research Institute for Nanotechnology, University of Twente, 7500 AE Enschede, Netherlands
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Jack A.M. Fransen,
Jack A.M. Fransen
2Department of Cell Biology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
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Petra H.M. Bovee-Geurts,
Petra H.M. Bovee-Geurts
3Department of Medical Biochemistry, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
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Frank N. van Leeuwen,
Frank N. van Leeuwen
1Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
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Niek F. Van Hulst,
Niek F. Van Hulst
5Applied Optics Group, Department of Science and Technology, Molecular Engineering Sensors and Actuators Research Institute for Nanotechnology, University of Twente, 7500 AE Enschede, Netherlands
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Carl G. Figdor
Carl G. Figdor
1Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
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Alessandra Cambi
1Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
Frank de Lange
1Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
Noortje M. van Maarseveen
4Department of Virology, University Medical Center Utrecht, 3508 GA Utrecht, Netherlands
Monique Nijhuis
4Department of Virology, University Medical Center Utrecht, 3508 GA Utrecht, Netherlands
Ben Joosten
1Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
Erik M.H.P. van Dijk
5Applied Optics Group, Department of Science and Technology, Molecular Engineering Sensors and Actuators Research Institute for Nanotechnology, University of Twente, 7500 AE Enschede, Netherlands
Bärbel I. de Bakker
5Applied Optics Group, Department of Science and Technology, Molecular Engineering Sensors and Actuators Research Institute for Nanotechnology, University of Twente, 7500 AE Enschede, Netherlands
Jack A.M. Fransen
2Department of Cell Biology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
Petra H.M. Bovee-Geurts
3Department of Medical Biochemistry, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
Frank N. van Leeuwen
1Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, Netherlands
Niek F. Van Hulst
5Applied Optics Group, Department of Science and Technology, Molecular Engineering Sensors and Actuators Research Institute for Nanotechnology, University of Twente, 7500 AE Enschede, Netherlands
Carl G. Figdor
1Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, 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: [email protected]
The online version of this article contains supplemental material.
Received:
June 20 2003
Accepted:
November 07 2003
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2004
J Cell Biol (2004) 164 (1): 145–155.
Article history
Received:
June 20 2003
Accepted:
November 07 2003
Citation
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; Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells . J Cell Biol 5 January 2004; 164 (1): 145–155. doi: https://doi.org/10.1083/jcb.200306112
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