HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 38, 32811-32820, September 23, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/38/32811    most recent M503457200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Su, Y. Articles by Martinez-Pomares, L. Search for Related Content PubMed PubMed Citation Articles by Su, Y. Articles by Martinez-Pomares, L. Social Bookmarking                      What's this?

Glycosylation Influences the Lectin Activities of the Macrophage Mannose Receptor^*

Yunpeng Su1, Talitha Bakker, James Harris2, Clarence Tsang, Gordon D. Brown3, Mark R. Wormald, Siamon Gordon, Raymond A. Dwek, Pauline M. Rudd4, and Luisa Martinez-Pomares5

From the Glycobiology Institute and the Biochemistry Department, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom and the Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom

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 SO₄-3-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.

Received for publication, March 30, 2005 , and in revised form, June 9, 2005.

^* This work was supported by the Medical Research Council and the Edward P. Abraham Research Fund.

¹ Present address: Whitehead Inst. for Medical Research, Nine Cambridge Centre, Cambridge, MA 02142.

² Present address: Dept. of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131.

³ Present address: Inst. of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, Cape Town, South Africa.

⁴ To whom correspondence may be addressed. Tel.: 44-1865-275-782; Fax: 44-1865-275-216; E-mail: pauline.rudd{at}bioch.ox.ac.uk. ⁵ To whom correspondence may be addressed. Tel.: 44-1865-275-531; Fax: 44-1865-275-515; E-mail: luisa.martinez-pomares{at}pathology.ox.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Lai, O. K. Bernhard, S. G. Turville, A. N. Harman, J. Wilkinson, and A. L. Cunningham Oligomerization of the Macrophage Mannose Receptor Enhances gp120-mediated Binding of HIV-1 J. Biol. Chem., April 24, 2009; 284(17): 11027 - 11038. [Abstract] [Full Text] [PDF]

				S. Rifat, T. J. Kang, D. Mann, L. Zhang, A. C. Puche, N. M. Stamatos, S. E. Goldblum, R. Brossmer, and A. S. Cross Expression of sialyltransferase activity on intact human neutrophils J. Leukoc. Biol., October 1, 2008; 84(4): 1075 - 1081. [Abstract] [Full Text] [PDF]

				F. Marttila-Ichihara, R. Turja, M. Miiluniemi, M. Karikoski, M. Maksimow, J. Niemela, L. Martinez-Pomares, M. Salmi, and S. Jalkanen Macrophage mannose receptor on lymphatics controls cell trafficking Blood, July 1, 2008; 112(1): 64 - 72. [Abstract] [Full Text] [PDF]

				J. Boskovic, J. N. Arnold, R. Stilion, S. Gordon, R. B. Sim, A. Rivera-Calzada, D. Wienke, C. M. Isacke, L. Martinez-Pomares, and O. Llorca Structural Model for the Mannose Receptor Family Uncovered by Electron Microscopy of Endo180 and the Mannose Receptor J. Biol. Chem., March 31, 2006; 281(13): 8780 - 8787. [Abstract] [Full Text] [PDF]