Glycosylation influences the lectin activities of the macrophage mannose receptor

Yunpeng Su, Talitha Bakker, James Harris, Clarence Tsang, Gordon D. Brown, Mark R. Wormald, Siamon Gordon, Raymond A. Dwek, Pauline M. Rudd, Luisa Martinez-Pomares

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The mannose receptor (MR) is a heavily glycosylated endocytic receptor that recognizes both mannosylated and sulfated ligands through its C-type lectin domains and cysteine-rich (CR) domain, respectively. Differential binding properties have been described for MR isolated from different sources, and we hypothesized that this could be due to altered glycosylation. Using MR transductants and purified MR, we demonstrate that glycosylation differentially affects both MR lectin activities. MR transductants generated in glycosylation mutant cell lines lacked most mannose internalization activity, but could internalize sulfated glycans. Accordingly, purified MR bearing truncated Man5-GlcNAc2 glycans (Man5-MR) or non-sialylated complex glycans (SA0-MR) did not bind mannosylated glycans, but could recognize SO4-S-Gal in vitro. Additional studies showed that, although mannose recognition was largely independent of the oligomerization state of the protein, recognition of sulfated carbohydrates was mostly mediated by self-associated MR and that, in SA0-MR, there was a higher proportion of oligomeric MR. These results suggest that self-association could lead to multiple presentation of CR domains and enhanced avidity for sulfated sugars and that non-sialylated MR is predisposed to oligomerize. Therefore, the glycosylation of MR, terminal sialylation in particular, could influence its binding properties at two levels, (i) It is required for mannose recognition; and (ii) it modulates the tendency of MR to self-associate, effectively regulating the avidity of the CR domain for sulfated sugar ligands.

Original languageEnglish
Pages (from-to)32811-32820
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number38
DOIs
Publication statusPublished - 23 Sep 2005
Externally publishedYes

Cite this

Su, Y., Bakker, T., Harris, J., Tsang, C., Brown, G. D., Wormald, M. R., ... Martinez-Pomares, L. (2005). Glycosylation influences the lectin activities of the macrophage mannose receptor. Journal of Biological Chemistry, 280(38), 32811-32820. https://doi.org/10.1074/jbc.M503457200
Su, Yunpeng ; Bakker, Talitha ; Harris, James ; Tsang, Clarence ; Brown, Gordon D. ; Wormald, Mark R. ; Gordon, Siamon ; Dwek, Raymond A. ; Rudd, Pauline M. ; Martinez-Pomares, Luisa. / Glycosylation influences the lectin activities of the macrophage mannose receptor. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 38. pp. 32811-32820.
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abstract = "The mannose receptor (MR) is a heavily glycosylated endocytic receptor that recognizes both mannosylated and sulfated ligands through its C-type lectin domains and cysteine-rich (CR) domain, respectively. Differential binding properties have been described for MR isolated from different sources, and we hypothesized that this could be due to altered glycosylation. Using MR transductants and purified MR, we demonstrate that glycosylation differentially affects both MR lectin activities. MR transductants generated in glycosylation mutant cell lines lacked most mannose internalization activity, but could internalize sulfated glycans. Accordingly, purified MR bearing truncated Man5-GlcNAc2 glycans (Man5-MR) or non-sialylated complex glycans (SA0-MR) did not bind mannosylated glycans, but could recognize SO4-S-Gal in vitro. Additional studies showed that, although mannose recognition was largely independent of the oligomerization state of the protein, recognition of sulfated carbohydrates was mostly mediated by self-associated MR and that, in SA0-MR, there was a higher proportion of oligomeric MR. These results suggest that self-association could lead to multiple presentation of CR domains and enhanced avidity for sulfated sugars and that non-sialylated MR is predisposed to oligomerize. Therefore, the glycosylation of MR, terminal sialylation in particular, could influence its binding properties at two levels, (i) It is required for mannose recognition; and (ii) it modulates the tendency of MR to self-associate, effectively regulating the avidity of the CR domain for sulfated sugar ligands.",
author = "Yunpeng Su and Talitha Bakker and James Harris and Clarence Tsang and Brown, {Gordon D.} and Wormald, {Mark R.} and Siamon Gordon and Dwek, {Raymond A.} and Rudd, {Pauline M.} and Luisa Martinez-Pomares",
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Su, Y, Bakker, T, Harris, J, Tsang, C, Brown, GD, Wormald, MR, Gordon, S, Dwek, RA, Rudd, PM & Martinez-Pomares, L 2005, 'Glycosylation influences the lectin activities of the macrophage mannose receptor', Journal of Biological Chemistry, vol. 280, no. 38, pp. 32811-32820. https://doi.org/10.1074/jbc.M503457200

Glycosylation influences the lectin activities of the macrophage mannose receptor. / Su, Yunpeng; Bakker, Talitha; Harris, James; Tsang, Clarence; Brown, Gordon D.; Wormald, Mark R.; Gordon, Siamon; Dwek, Raymond A.; Rudd, Pauline M.; Martinez-Pomares, Luisa.

In: Journal of Biological Chemistry, Vol. 280, No. 38, 23.09.2005, p. 32811-32820.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Glycosylation influences the lectin activities of the macrophage mannose receptor

AU - Su, Yunpeng

AU - Bakker, Talitha

AU - Harris, James

AU - Tsang, Clarence

AU - Brown, Gordon D.

AU - Wormald, Mark R.

AU - Gordon, Siamon

AU - Dwek, Raymond A.

AU - Rudd, Pauline M.

AU - Martinez-Pomares, Luisa

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N2 - The mannose receptor (MR) is a heavily glycosylated endocytic receptor that recognizes both mannosylated and sulfated ligands through its C-type lectin domains and cysteine-rich (CR) domain, respectively. Differential binding properties have been described for MR isolated from different sources, and we hypothesized that this could be due to altered glycosylation. Using MR transductants and purified MR, we demonstrate that glycosylation differentially affects both MR lectin activities. MR transductants generated in glycosylation mutant cell lines lacked most mannose internalization activity, but could internalize sulfated glycans. Accordingly, purified MR bearing truncated Man5-GlcNAc2 glycans (Man5-MR) or non-sialylated complex glycans (SA0-MR) did not bind mannosylated glycans, but could recognize SO4-S-Gal in vitro. Additional studies showed that, although mannose recognition was largely independent of the oligomerization state of the protein, recognition of sulfated carbohydrates was mostly mediated by self-associated MR and that, in SA0-MR, there was a higher proportion of oligomeric MR. These results suggest that self-association could lead to multiple presentation of CR domains and enhanced avidity for sulfated sugars and that non-sialylated MR is predisposed to oligomerize. Therefore, the glycosylation of MR, terminal sialylation in particular, could influence its binding properties at two levels, (i) It is required for mannose recognition; and (ii) it modulates the tendency of MR to self-associate, effectively regulating the avidity of the CR domain for sulfated sugar ligands.

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