Proteomic analysis of DC-SIGN on dendritic cells detects tetramers required for ligand binding but no association with CD4.

The Journal of Biological Chemistry
Oliver K BernhardAnthony L Cunningham

Abstract

DC-SIGN (dendritic cell specific intracellular adhesion molecule 3 grabbing non-integrin) or CD209 is a type II transmembrane protein and one of several C-type lectin receptors expressed by dendritic cell subsets, which bind to high mannose glycoproteins promoting their endocytosis and potential degradation. DC-SIGN also mediates attachment of HIV to dendritic cells and binding to this receptor can subsequently lead to endocytosis or enhancement of CD4/CCR5-dependent infection. The latter was proposed to be facilitated by an interaction between DC-SIGN and CD4. Endocytosis of HIV virions does not necessarily lead to their complete degradation. A proportion of the virions remain infective and can be later presented to T cells mediating their infection in trans. Previously, the extracellular domain of recombinant DC-SIGN has been shown to assemble as tetramers and in the current study we use a short range covalent cross-linker and show that DC-SIGN exists as tetramers on the surface of immature monocyte-derived dendritic cells. There was no evidence of direct binding between DC-SIGN and CD4 either by cross-linking or by fluorescence resonance energy transfer measurements suggesting that there is no constitutive association of the...Continue Reading

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Citations

May 7, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ui-Soon KhooC L Steve Lin
Jun 14, 2005·Current Opinion in Immunology·Alessandra Cambi, Carl G Figdor
Feb 20, 2009·The Journal of Biological Chemistry·Joey LaiAnthony L Cunningham
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Aug 16, 2005·Expert Review of Proteomics·Oliver K BernhardAnthony L Cunningham
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Mar 30, 2006·International Immunology·Irina CaminschiMark D Wright
Jul 30, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Najla NasrAnthony L Cunningham
Aug 1, 2020·Frontiers in Cellular and Infection Microbiology·Malgorzata E MnichNina M van Sorge
Apr 14, 2021·Nature Communications·Jake W RhodesAndrew N Harman

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