Galectin-1

From CFGparadigms

Galectin-1 is the best-studied of the prototypic galectins. The crystal structure of Galectin-1 is known, and was the first crystal structure identified for a prototypic galectin.
In addition, Galectin-1...

• was the first prototypic galectin for which a function was identified.
• binds novel N- and O-glycan determinants that are involved in cell signaling^{[1][2][3][4][5]}.
• was the first prototypic galectin that was genetically ablated in mice; galectin-1 knockout mice have distinct phenotypes, including aberrant T lymphocyte expansion and increased susceptibility to autoimmune disease ^[6].
• is the only prototypic galectin that has been administered in animal models of disease to assess therapeutic potential ^[7]
• selectively regulates Th1, Th2 and Th17 cell survival^[8]
• has novel dynamics and functions regarding it oxidized versus reduced status, as well as its dimerization status^[9][1].
• is involved in lymphocyte trafficking and leukocyte recruitment^[4][10].
• promotes the differentiation of tolerogenic dendritic cells and plays a pivotal role in fetomaternal tolerance ^[11][12]
• contributes to tumor cell evasion of immune responses.^[13]
• demonstrates novel distributions in muscle cells versus non-muscle cells^[14].
• has ligands that are modulated by their differential sialylation, which is also associated with glycoprotein positioning in membranes^[15].

Contents 1 CFG Participating Investigators contributing to the understanding of this paradigm 2 Progress toward understanding this GBP paradigm 2.1 Carbohydrate ligands 2.2 Cellular expression of GBP and ligands 2.3 Biosynthesis of ligands 2.4 Structure 2.5 Biological roles of GBP-ligand interaction 3 CFG resources used in investigations 3.1 Glycan profiling 3.2 Glycogene microarray 3.3 Knockout mouse lines 3.4 Glycan array 4 Related GBPs 5 References 6 Acknowledgements

CFG Participating Investigators contributing to the understanding of this paradigm

CFG Participating Investigators (PIs) contributing to the understanding of Galectin-1 include: Linda Baum, C. Fred Brewer, Richard Cummings, Anne Dell, Ten Feizi, M.G. Finn, Thomas Gerken, Benhur Lee, J. Michael Pierce, Mauro Perretti, Gabriel Rabinovich, James Rini, Sachiko Sato, Gerald Schwarting, Pamela Stanley, Victor Thijssen, Gerardo Vasta, John Wang

Progress toward understanding this GBP paradigm

This section documents what is currently known about Galectin-1, its carbohydrate ligand(s), and how they interact to mediate cell communication. Further information can be found in the GBP Molecule Pages for human and mouse Galectin-1 in the CFG database.

Carbohydrate ligands

The ligand of galectin-1 has been shown to be Galβ1-4GlcNAc (or LacNAc).

Cellular expression of GBP and ligands

Galectin-1 is expressed in many cell types including muscle, epithelial and endothelial cells. Within the immune system this GBP is considerably up-regulated in activated T lymphocytes, macrophages, uterine NK cells and regulatory T cells.

Biosynthesis of ligands

Structure

Galectin-1 can be found as a monomer as well as a non-covalent homodimer composed of subunits of 14.5 kDa, each containing an identical CRD.
Crosslinking of galectin-1 and complex biantennary N-glycans. Infinite chains of lectin dimers (cyan) are cross-linked through N-acetyllactosamine units located at the ends antennae (green/yellow) biantennary N-glycans.^[16]

Biological roles of GBP-ligand interaction

Galectin-1 is involved in immunoregulation, cytokine secretion, host-pathogen interactions, cell adhesion and migration and tumor-immune escape.

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 Galectin-1.

Glycan profiling

Glycan profiling of cells known to express Galectin-1 has been done by the CFG analytical core (e.g. T-lymphocytes).

Glycogene microarray

Knockout mouse lines

CFG-generated Galectin-1 knockout mice have been used to study the biological functions of this paradigm GBP. The phenotype of Galectin-1 knockout mice was analyzed by the CFG.

Glycan array

Investigators have made extensive use of carbohydrate compounds and glycan microarrays to study ligand binding specificity of galectin-1 (example). See all glycan array results for galectin-1 here.

Related GBPs

Galectins-2, -5, -7, -10, -11, -13, and -14

References

1. ↑ ^{1.0 1.1} Leppanen A, Stowell S, Blixt O, Cummings RD. Dimeric galectin-1 binds with high affinity to alpha2,3-sialylated and non-sialylated terminal N-acetyllactosamine units on surface-bound extended glycans. J Biol Chem 280, 5549-5562 (2005).
2. ↑ Earl LA, Bi S, Baum LG. N- and O-glycans modulate galectin-1 binding, CD45 signaling, and T cell death. J Biol Chem 285, 2232-2244 (2010).
3. ↑ Song X, et al. Novel fluorescent glycan microarray strategy reveals ligands for galectins. Chem Biol 16, 36-47 (2009).
4. ↑ ^{4.0 4.1} Cooper D, Norling LV, Perretti M. Novel insights into the inhibitory effects of Galectin-1 on neutrophil recruitment under flow. J Leukoc Biol 83, 1459-1466 (2008).
5. ↑ Stillman BN, et al. Galectin-3 and galectin-1 bind distinct cell surface glycoprotein receptors to induce T cell death. J Immunol 176, 778-789 (2006).
6. ↑ Rabinovich GA, Toscano MA. Turning "sweet" on immunity: galectin-glycan interactions in immune tolerance and inflammation. Nat Rev Immunol 9, 338-352 (2009).
7. ↑ Rabinovich GA, Daly G, Dreja H, Tailor H, Riera CM, Hirabayashi J, Chernajovsky Y. Recombinant galectin-1 and its genetic delivery suppress collagen-induced arthritis via T cell apoptosis. J Exp Med 190, 385-398 (1999)
8. ↑ Toscano MA, Bianco GA, Ilarregui JM, Croci DO, Correale J, Hernandez JD, Zwirner NW, Poirier F, Riley EM, Baum LG, Rabinovich GA. Differential glycosylation of Th1, Th2 and Th17 effector cells selectively regulates susceptibility to cell death. Nat Immunol 8, 825-834 (2007).
9. ↑ Stowell SR, et al. Ligand reduces galectin-1 sensitivity to oxidative inactivation by enhancing dimer formation. J Biol Chem 284, 4989-4999 (2009).
10. ↑ Norling LV, Sampaio AL, Cooper D, Perretti M. Inhibitory control of endothelial galectin-1 on in vitro and in vivo lymphocyte trafficking. Faseb J 22, 682-690 (2008).
11. ↑ Ilarregui JM, Croci DO, Bianco GA, Toscano MA, Salatino M, Vermeulen ME, Geffner JR, Rabinovich GA.Nat Immunol 10, 981-991 (2009).
12. ↑ Blois SM, et al. A pivotal role for galectin-1 in fetomaternal tolerance. Nat Med 13,1450-1457 (2007).
13. ↑ Rubinstein N, Alvarez M, Zwirner NW, Toscano MA, Ilarregui JM, Bravo A, Mordoh J, Fainboim L, Podhajcer OL, Rabinovich GA. Cancer Cell 5, 241-251 (2004).
14. ↑ Dias-Baruffi M, et al. Differential expression of immunomodulatory galectin-1 in peripheral leukocytes and adult tissues and its cytosolic organization in striated muscle. Glycobiology In Press. (2010).
15. ↑ Cha SK, et al. Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1. Proc Natl Acad Sci U S A 105, 9805-9810 (2008).
16. ↑ Bourne et al. Crosslinking of mammalian lectin (galectin-1) by complex biantennary saccharides. Nat Struct Biol. 12:863-70 (1994).

Acknowledgements

The CFG is grateful to the following PIs for their contributions to this wiki page: Linda Baum, Yves Bourne, Richard Cummings, Ten Feizi, Gabriel Rabinovich