Macrophage galactose lectin (MGL)

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Macrophage galactose binding lectin (MGL) is the best studied of the multiple C-type lectins on macrophages [1][2]. It is also representative of the subclass of C-type lectins that bind galactose-related sugars. MGL consists of one CRD domain and contains cytoplasmic internalization motifs for endocytosis. No signaling properties have been described yet for MGL. Human MGL (CD301) and rat MGL are encoded by a single gene, whereas mice contain two MGL copies, mMGL-1 and mMGL-2 that differ in carbohydrate specificity [3][4][5].

Contents

CFG Participating Investigators contributing to the understanding of this paradigm

In addition to creating the knockout for the two mouse forms of MGL, PIs have been involved in extensive studies of binding specificity and mechanism of ligand binding as well as the role of the receptor in macrophage signaling.

  • PIs working on MGL include: Nicolai Bovin, Kurt Drickamer, Toshisuke Kawasaki, Cheng Liu, Yvette van Kooyk, Hui Wu
  • Non-PIs with who have used CFG resources to study MGL include: Siamon Gordon, Alan Saltiel
  • PIs working on MGL-related glycan-binding proteins (GBPs), particularly Mincle, include: Anthony dApice, Joshua Fierer, Rikard Holmdahl, Christopher O'Callaghan, Judy Teale, Christine Wells
  • Non-PIs with who have used resources to study related members of this paradigm group include: Roland Lang, Ulrich Maus, Gunnar Nilsson, Kenneth Rock

Progress toward understanding this GBP paradigm

This section documents what is currently known about MGL, its carbohydrate ligand(s), and how they interact to mediate cell communication. Further information about MGL can be found in its GBP Molecule Page in the CFG database.

Carbohydrate ligands

  • mMGL1 binds Lewis X and Lewis A structures, whereas mMGL2 recognizes N-acetylgalactosamine (GalNAc) and galactose, including the O-linked Tn-antigen and TF-antigen [3][4]
  • hMGL binds terminal α- and β-linked GalNAc residues on glycoproteins, glycolipids and bacterial LPS, including Tn antigen and GalNAcβ1-4GlcNAc-R (LDN) antigens [2][6][7][8]


Cellular expression of GBP and ligands

MGL is expressed on DCs and macrophages [5][9]

Biosynthesis of ligands


Structure


Biological roles of GBP-ligand interaction

  • MGL is a highly efficient internalization receptor [5][10]
  • hMGL regulates T-cell receptor mediated signaling and T-cell dependent cytokine responses [9]</ref>
  • mMGL1 promotes adipose tissue inflammation and insulin resistance [11]
  • mMGL2 promotes enhances both MHC class II and class I presentation antigen in DC [12]


CFG resources used in investigations

The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for MGL.

Glycan profiling


Glycogene microarray


Knockout mouse lines

Knockouts for one of the mouse orthologs of MGL was distributed by the CFG and the phenotype was analyzed.

Glycan array

The glycan-binding specificity of human and mouse versions of MGL have been analyzed by glycan array screening [6][4]. See all glycan array results for MGL here.

Related GBPs

Other C-type lectins on macrophages include the mannose receptor, mincle [13], macrophage C- type lectin (MCL), and dectin-1.

References

  1. Kawasaki T, Ii M, Kozutsumi Y and Yamashina I. 1986. Isolation and characterization of a receptor lectin specific for galactose/N-acetylgalactosamine from macrophages. Carbohydr Res. 151:197-206
  2. 2.0 2.1 Suzuki N, Yamamoto K, Toyoshima S, Osawa T and Irimura T. 1996. Molecular cloning and expression of cDNA encoding human macrophage C-type lectin. Its unique carbohydrate binding specificity for Tn antigen. J Immunol. 156:128-135
  3. 3.0 3.1 Tsuiji M, Fujimori M, Ohashi Y, Higashi N, Onami TM, Hedrick SM and Irimura T. 2002. Molecular cloning and characterization of a novel mouse macrophage C-type lectin, mMGL2, which has a distinct carbohydrate specificity from mMGL1. J Biol Chem. 277:28892-28901
  4. 4.0 4.1 4.2 Singh SK, Streng-Ouwehand I, Litjens M, Weelij DR, Garca-Vallejo JJ, van Vliet SJ, Saeland E, van Kooyk Y. 2009. Characterization of murine MGL1 and MGL2 C-type lectins: distinct glycan specificities and tumor binding properties. Mol Immunol 46: 1240-1249
  5. 5.0 5.1 5.2 Higashi N, Fujioka K, Denda-Nagai K, Hashimoto S, Nagai S, Sato T, Fujita Y, Morikawa A, Tsuiji M, Miyata-Takeuchi M, Sano Y, Suzuki N, Yamamoto K, Matsushima K and Irimura T. 2002. The macrophage C-type lectin specific for galactose/N-acetylgalactosamine is an endocytic receptor expressed on monocyte-derived immature dendritic cells. J Biol Chem. 277:20686-20693
  6. 6.0 6.1 van Vliet SJ, van Liempt E, Saeland E, Aarnoudse CA, Appelmelk B, Irimura T, Geijtenbeek TB, Blixt O, Alvarez R, van Die I and van Kooyk Y. 2005. Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells. Int Immunol. 17:661-669
  7. van Sorge NM, Bleumink NM, van Vliet SJ, Saeland E, van der Pol WL, van Kooyk Y and van Putten JP. 2009. N-glycosylated proteins and distinct lipooligosaccharide glycoforms of Campylobacter jejuni target the human C-type lectin receptor MGL. Cell Microbiol. 11:1768-1781
  8. Saeland E, van Vliet SJ, Backstrom M, van den Berg VC, Geijtenbeek TB, Meijer GA and van Kooyk Y. 2007. The C-type lectin mgl expressed by dendritic cells detects glycan changes on Muc1 in colon carcinoma. Cancer Immunol Immunother. 56:1225-1236
  9. 9.0 9.1 van Vliet SJ, Gringhuis SI, Geijtenbeek TB and van Kooyk Y. 2006. Regulation of effector T cells by antigen-presenting cells via interaction of the C-type lectin MGL with CD45. Nat Immunol. 7:1200-1208
  10. Valladeau J, Duvert-Frances V, Pin JJ, Kleijmeer MJ, Ait-Yahia S, Ravel O, Vincent C, Vega F, Jr., Helms A, Gorman D, Zurawski SM, Zurawski G, Ford J and Saeland S. 2001. Immature human dendritic cells express asialoglycoprotein receptor isoforms for efficient receptor-mediated endocytosis. J Immunol. 167:5767-5774
  11. Westcott DJ, Delproposto JB, Geletka LM, Wang T, Singer K, Saltiel AR, Lumeng CN. 2009. MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity. J Exp Med 206: 3143-56
  12. Singh SK, Streng-Ouwehand I, Litjens M, Kalay H, Saeland E, Van Kooyk Y. 2010. Tumour-associated glycan modifications of antigen enhance MGL2 dependent uptake and MHC class I restricted CD8 T cell responses. Int. J. Cancer, in press
  13. Wells CA, Salvage-Jones JA, Li X, Hitchens K, Butcher S, Murray RZ, Beckhouse AG, Lo YL, Manzanero S, Cobbold C, Schroder K, Ma B, Orr S, Stewart L, Lebus D, Sobieszczuk P, Hume DA, Stow J, Blanchard H, Ashman RB. 2008. The macrophage-inducible C-type lectin, mincle, is an essential component of the innate immune response to Candida albicans. J Immunol 180: 7404-7413


Acknowledgements

The CFG is grateful to the following PIs for their contributions to this wiki page: Kurt Drickamer, Yvette van Kooyk

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