The Cysteine-Rich Domain of the Macrophage Mannose Receptor Is a Multispecific Lectin That Recognizes Chondroitin Sulfates a and B and Sulfated Oligosaccharides of Blood Group Lewisa and Lewisx Types in Addition to the Sulfated <i>N</i>-Glycans of Lutropin

Leteux, Christine; Chai, Wengang; Loveless, R W; Yuen, Chun-Ting; Uhlin‐Hansen, Lars; Combarnous, Yves; Janković, Mila; Maric, Svetlana C.; Misulovin, Ziva; Nussenzweig, Michel C.; Feizi, Ten

doi:10.1084/jem.191.7.1117

Cited by 158 publications

(135 citation statements)

References 51 publications

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…As described in Ref. 35, carbohydrates displaying SO 4 at position 6 were poorly recognized. D, binding of sMR-HA to mannan is salt-independent, calcium-dependent, and competed by mannose and fucose but not galactose.…”

mentioning

confidence: 87%

Structural Model for the Mannose Receptor Family Uncovered by Electron Microscopy of Endo180 and the Mannose Receptor

Boskovic

Arnold

Stilion

et al. 2006

Journal of Biological Chemistry

108

View full text Add to dashboard Cite

The mannose receptor family comprises four members in mammals, Endo180 (CD280), DEC-205 (CD205), phospholipase A 2 receptor (PLA 2 R) and the mannose receptor (MR, CD206), whose extracellular portion contains a similar domain arrangement: an N-terminal cysteine-rich domain (CysR) followed by a single fibronectin type II domain (FNII) and 8 -10 C-type lectin-like domains (CTLDs). These proteins mediate diverse functions ranging from extracellular matrix turnover through collagen uptake to homeostasis and immunity based on sugar recognition. Endo180 and the MR are multivalent transmembrane receptors capable of interacting with multiple ligands; in both receptors FNII recognizes collagens, and a single CTLD retains lectin activity (CTLD2 in Endo180 and CTLD4 in MR). It is expected that the overall conformation of these multivalent molecules would deeply influence their function as the availability of their binding sites could be altered under different conditions. However, conflicting reports have been published on the three-dimensional arrangement of these receptors. Here, we have used single particle electron microscopy to elucidate the three-dimensional organization of the MR and Endo180. Strikingly, we have found that both receptors display distinct threedimensional structures, which are, however, conceptually very similar: a bent and compact conformation built upon interactions of the CysR domain and the lone functional CTLD. Biochemical and electron microscopy experiments indicate that, under a low pH mimicking the endosomal environment, both MR and Endo180 experience large conformational changes. We propose a structural model for the mannose receptor family where at least two conformations exist that may serve to regulate differences in ligand selectivity.The mannose receptor (MR 4 and CD206), together with Endo180 (also known as the urokinase-type plasminogen activator receptor-associated protein (uPARAP) and CD280), the dendritic cell receptor DEC-205 (CD205) and the M-type phospholipase A 2 receptor (PLA 2 R) encompass the mannose receptor family of endocytic receptors (1, 2). The members of this family are unique within the superfamily of C-type lectins as these alone contain multiple C-type lectin-like domains (CTLDs) within a single polypeptide backbone. All these receptors are recycled between the plasma membrane and the endosomal apparatus and mediate the uptake of extracellular ligands for intracellular delivery (2). Recently, an avian structural homologue of the mammalian mannose receptor family members, FcRY, has been discovered to function as a yolk sac IgY receptor (3).The MR was originally described as a transmembrane receptor that recognized saccharide chains terminating in mannose and designated as the macrophage mannose receptor. Since its expression was found not to be restricted to macrophages, it is now known as MR (2). MR executes important roles in the immune system by functioning as a pattern recognition receptor toward a wide range of pathogens. Other members of the family were found ...

show abstract

mentioning

confidence: 87%

Structural Model for the Mannose Receptor Family Uncovered by Electron Microscopy of Endo180 and the Mannose Receptor

Boskovic

Arnold

Stilion

et al. 2006

Journal of Biological Chemistry

108

View full text Add to dashboard Cite

show abstract

“…The eight membrane-proximal carbohydrate recognition domains (CRDs) of MR bind mannose-, N-acetylglucosamine-, and fucose-terminating oligosaccharides, which are commonly found on the cell wall of bacteria, yeast, and parasites, but are rarely seen in sufficient densities in terminal positions of mammalian oligosaccharides (1). For the NH 2 -terminal cysteinrich domain of MR (Cys-MR), only endogenous ligands have described to date, which terminate in 4-sulfated N-acetylgalactoseamine and include sulfated carbohydrates on pituitary hormones, chondroitin sulfate, and sulfated blood group chains (2,3). Whereas the role of Cys-MR ligand binding in innate immunity is not yet well defined, the fate of CRD ligands is well established in macrophages and dendritic cells.…”

Section: T He 180-kda Mannose Receptor (Mr)mentioning

confidence: 99%

Dermal Microvascular Endothelial Cells Express the 180-kDa Macrophage Mannose Receptor In Situ and In Vitro

Gröger¹,

Holnthoner²,

Maurer

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

Expression of the 180-kDa mannose receptor (MR) is mainly found on cells of the macrophage lineage. MR mediates the uptake of micro-organisms and host-derived glycoproteins. We demonstrate that endothelium of the human skin in situ and dermal microvascular endothelial cells (DMEC) in vitro expressed MR at both the protein and mRNA levels. In contrast, HUVEC were consistently negative for MR expression. DMEC internalized dextran as well as Escherichia coli by the way of MR into acidic phagosomes, only a few of which fused with CD63- and lysosomal-associated membrane glycoprotein-2-positive lysosomes. This contrasts with the situation in monocyte-derived dendritic cells, where almost all of the MR-Ag complexes reached CD63- and lysosomal-associated membrane glycoprotein-2-positive compartments, indicating differences in the phagolysosomal fusion rate between DMEC and dendritic cells. In conclusion, DMEC express functional MR, a finding that corroborates a role of skin endothelium in Ag capture/clearing.

show abstract

“…1A). The cysteine-rich (CR) domain recognises sugars terminated in SO 4-3 -galactose (Gal) or SO 4-3/4-N-acetylgalactosamine (GalNAc) [13,14], while mannose (Man), together with fucose (Fuc) and N-acetylglucosamine (GlcNAc), recognition is mediated by C-type lectin-like domain (CTLD) 4 with co-operation from CTLD5 [15]. A single fibronectin type II (FNII) domain is located between the CR domain and the CTLD [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Carbohydrate‐independent recognition of collagens by the macrophage mannose receptor

Martı́nez-Pomares¹,

Wienke

Stillion³

et al. 2006

Eur J Immunol

129

130

View full text Add to dashboard Cite

Mannose receptor (MR) is the best characterised member of a family of four endocytic molecules that share a common domain structure; a cysteine-rich (CR) domain, a fibronectin-type II (FNII) domain and tandemly arranged C-type lectin-like domains (CTLD, eight in the case of MR). Two distinct lectin activities have been described for MR. The CR domain recognises sulphated carbohydrates while the CTLD mediate binding to mannose, fucose or N-acetylglucosamine. FNII domains are known to be important for collagen binding and this has been studied in the context of two members of the MR family, Endo180 and the phospholipase A 2 receptor. Here, we have investigated whether the broad and effective lectin activity mediated by the CR domain and CTLD of MR is favoured to the detriment of FNII-mediated interaction(s). We show that MR is able to bind and internalise collagen in a carbohydrate-independent manner and that MR deficient macrophages have a marked defect in collagen IV and gelatin internalisation. These data have major implications at the molecular level as there are now three distinct ligand-binding sites described for MR. Furthermore our findings extend the range of endogenous ligands recognised by MR, a molecule firmly placed at the interface between homeostasis and immunity.

show abstract

The Cysteine-Rich Domain of the Macrophage Mannose Receptor Is a Multispecific Lectin That Recognizes Chondroitin Sulfates a and B and Sulfated Oligosaccharides of Blood Group Lewisa and Lewisx Types in Addition to the Sulfated N-Glycans of Lutropin

Cited by 158 publications

References 51 publications

Structural Model for the Mannose Receptor Family Uncovered by Electron Microscopy of Endo180 and the Mannose Receptor

Structural Model for the Mannose Receptor Family Uncovered by Electron Microscopy of Endo180 and the Mannose Receptor

Dermal Microvascular Endothelial Cells Express the 180-kDa Macrophage Mannose Receptor In Situ and In Vitro

Carbohydrate‐independent recognition of collagens by the macrophage mannose receptor

Contact Info

Product

Resources

About