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

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

doi:10.1083/jcb.200306112

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

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

Research output: Contribution to journal › Article › peer-review

199 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	145-55
Number of pages	11
Journal	The Journal of Cell Biology
Volume	164
Issue number	1
DOIs	https://doi.org/10.1083/jcb.200306112
Publication status	Published - 5 Jan 2004
Externally published	Yes

Keywords

Cell Adhesion Molecules/immunology
Cell Membrane/metabolism
Cells, Cultured
Dendritic Cells/metabolism
Endocytosis/physiology
HIV Infections/immunology
HIV-1/pathogenicity
Humans
Immunohistochemistry
Lectins, C-Type/immunology
Membrane Microdomains/metabolism
Microscopy, Electron
Monocytes/metabolism
Protein Structure, Tertiary/physiology
RNA Virus Infections/immunology
Receptors, Cell Surface/immunology
Receptors, Virus/immunology

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10.1083/jcb.200306112

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Cambi, A., de Lange, F., van Maarseveen, N. M., Nijhuis, M., Joosten, B., van Dijk, E. M. H. P., de Bakker, B. I., Fransen, J. A. M., Bovee-Geurts, P. H. M., van Leeuwen, F. N., Van Hulst, N. F., & Figdor, C. G. (2004). Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells. The Journal of Cell Biology, 164(1), 145-55. https://doi.org/10.1083/jcb.200306112

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

abstract = "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.",

keywords = "Cell Adhesion Molecules/immunology, Cell Membrane/metabolism, Cells, Cultured, Dendritic Cells/metabolism, Endocytosis/physiology, HIV Infections/immunology, HIV-1/pathogenicity, Humans, Immunohistochemistry, Lectins, C-Type/immunology, Membrane Microdomains/metabolism, Microscopy, Electron, Monocytes/metabolism, Protein Structure, Tertiary/physiology, RNA Virus Infections/immunology, Receptors, Cell Surface/immunology, Receptors, Virus/immunology",

author = "Alessandra Cambi and {de Lange}, Frank and {van Maarseveen}, {Noortje M} and Monique Nijhuis and Ben Joosten and {van Dijk}, {Erik M H P} and {de Bakker}, {B{\"a}rbel I} and Fransen, {Jack A M} and Bovee-Geurts, {Petra H M} and {van Leeuwen}, {Frank N} and {Van Hulst}, {Niek F} and Figdor, {Carl G}",

year = "2004",

month = jan,

day = "5",

doi = "10.1083/jcb.200306112",

language = "English",

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Cambi, A, de Lange, F, van Maarseveen, NM, Nijhuis, M, Joosten, B, van Dijk, EMHP, de Bakker, BI, Fransen, JAM, Bovee-Geurts, PHM, van Leeuwen, FN, Van Hulst, NF & Figdor, CG 2004, 'Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells', The Journal of Cell Biology, vol. 164, no. 1, pp. 145-55. https://doi.org/10.1083/jcb.200306112

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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

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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 - http://www.scopus.com/inward/record.url?scp=0347122962&partnerID=8YFLogxK

U2 - 10.1083/jcb.200306112

DO - 10.1083/jcb.200306112

M3 - Article

C2 - 14709546

VL - 164

SP - 145

EP - 155

JO - The Journal of Cell Biology

JF - The Journal of Cell Biology

SN - 0021-9525

IS - 1

ER -

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

Abstract

Keywords

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