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Galectins as Pattern Recognition Receptors: Structure, Function, and Evolution

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Current Topics in Innate Immunity II

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 946))

Abstract

Galectins constitute an evolutionary conserved family of ß-galactoside-binding proteins, ubiquitous in mammals and other vertebrate taxa, invertebrates, and fungi. Since their discovery in the 1970s, their biological roles, initially understood as limited to recognition of carbohydrate ligands in embryogenesis and development, have expanded in recent years by the discovery of their immunoregulatory activities. A gradual paradigm shift has taken place in the past few years through the recognition that galectins also bind glycans on the surface of potentially pathogenic microbes, and function as recognition and effector factors in innate immunity. Further, an additional level of functional complexity has emerged with the most recent findings that some parasites “subvert” the recognition roles of the vector/host galectins for successful attachment or invasion.

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References

  • Ahmed, H. and Vasta, G.R. (1994) Galectins: conservation of functionally and structurally relevant amino acid residues defines two types of carbohydrate recognition domains. Glycobiology 4, 548

    Article  Google Scholar 

  • Ahmed, H. and Vasta, G.R. (2008) Unlike mammalian GRIFIN, the zebrafish homologue (DrGRIFIN) represents a functional carbohydrate-binding galectin. Biochem Biophys Res Commun 371, 355

    Article  CAS  Google Scholar 

  • Ahmed, H., Bianchet, M.A., Amzel, L.M., Hirabayashi, J., Kasai, K.-I., Giga-Hama, Y., Tohda, H. and Vasta, G.R. (2002) Novel carbohydrate specificity of the 16-kDa galectin from Caenorhabditis elegans: binding to blood group precursor oligosaccharides (type 1, type 2, Talpha, and Tbeta) and gangliosides. Glycobiology 12, 461

    Article  Google Scholar 

  • Ahmed, H., Du, S.-J., O’Leary, N. and Vasta, G.R. (2004) Biochemical and molecular characterization of galectins from zebrafish (Danio rerio): notochord-specific expression of a prototype galectin during early embryogenesis. Glycobiology 14, 232

    Google Scholar 

  • Bianchet, M.A., Ahmed, H., Vasta, G.R. and Amzel, L.M. (2000) Soluble beta-galactosyl-binding lectin (galectin) from toad ovary: crystallographic studies of two protein-sugar complexes. Proteins 40, 388

    Article  Google Scholar 

  • Brewer, C.F., Miceli, M.C. and Baum, L.G. (2002) Clusters, bundles, arrays and lattices: novel mechanisms for lectin-saccharide-mediated cellular interactions. Curr Opin Struct Biol 12, 623

    Article  Google Scholar 

  • Cho, M. and Cummings, R.D. (1995) Galectin-1, a beta-galactoside -binding lectin in Chinese hamster ovary cells. II. Localization and biosynthesis. J Biol Chem 270, 5212

    Article  Google Scholar 

  • Cleves, A.E., Cooper, D.N., Barondes, S.H. and Kelly, R.B. (1996) A new pathway for protein export in Saccharomyces cerevisiae. J Cell Biol 133, 1026

    Article  Google Scholar 

  • Colnot, C., Fowlis, D., Ripoche, M.A., Bouchaert, I. and Poirier, F. (1998) Embryonic implantation in galectin 1/galectin 3 double mutant mice. Dev Dyn 211, 306-313

    Article  PubMed  CAS  Google Scholar 

  • Colnot, C., Ripoche, M., Fowlis, D., Cannon, V., Scaerou, F., Cooper, D.N.W. and Poirier, F. (1997) The role of galectins in mouse development. Trends Glycosci. Glycotechnol. 9, 31-40

    Article  CAS  Google Scholar 

  • Colnot, C., Sidhu, S.S., Balmain, N. and Poirier, F. (2001) Uncoupling of chondrocyte death and vascular invasion in mouse galectin 3 null mutant bones. Dev Biol 229, 214

    Article  CAS  Google Scholar 

  • Cooper, D.N.W. (2002) Galectinomics: finding themes in complexity. Biochim. Biophys. Acta 1572, 231

    Article  Google Scholar 

  • Cooper, D.N., Massa, S.M. and Barondes, S.H. (1991) Endogenous muscle lectin inhibits myoblast adhesion to laminin. J Cell Biol 115, 1448

    Google Scholar 

  • Dam, T.K. and Brewer, C.F. (2008) Effects of clustered epitopes in multivalent ligand-receptor interactions. Biochemistry 47, 8476

    Article  CAS  Google Scholar 

  • Dias-Baruffi, M., Stowell, S.R., Song, S.-C., Arthur, C.M., Cho, M., Rodrigues, L.C., Montes, M.A.B., Rossi, M.A., James, J.A., McEver, R.P. and Cummings, R.D. (2010) Differential expression of immunomodulatory galectin-1 in peripheral leukocytes and adult tissues and its cytosolic organization in striated muscle. Glycobiology 20, 507

    Article  PubMed  CAS  Google Scholar 

  • Fang, R., Mantle, M. and Ceri, H. (1993) Characterization of quail intestinal mucin as a ligand for endogenous quail lectin. Biochem J 293, 867

    PubMed  CAS  Google Scholar 

  • Fogel, S., Guittaut, M., Legrand, A., Monsigny, M. and Hebert, E. (1999) The tat protein of HIV-1 induces galectin-3 expression. Glycobiology 9, 383-387

    Article  PubMed  CAS  Google Scholar 

  • Fowlis, D., Colnot, C., Ripoche, M.A. and Poirier, F. (1995) Galectin-3 is expressed in the notochord, developing bones, and skin of the postimplantation mouse embryo. Dev Dyn 203, 251

    Article  Google Scholar 

  • Gabius, H.J. (1997) Animal lectins. Eur J Biochem 243, 543

    Article  PubMed  CAS  Google Scholar 

  • Georgiadis, V., Stewart, H.J.S., Pollard, H.J., Tavsanoglu, Y., Prasad, R., Horwood, J., Deltour, L., Goldring, K., Poirier, F. and Lawrence-Watt, D.J. (2007) Lack of galectin-1 results in defects in myoblast fusion and muscle regeneration. Dev Dyn 236, 1024

    Article  CAS  Google Scholar 

  • Gorski, J.P., Liu, F.-T., Artigues, A., Castagna, L.F. and Osdoby, P. (2002) New alternatively spliced form of galectin-3, a member of the beta-galactoside -binding animal lectin family, contains a predicted transmembrane-spanning domain and a leucine zipper motif. J Biol Chem 277, 18848

    Article  CAS  Google Scholar 

  • Harvell, C.D., Kim, K., Burkholder, J.M., Colwell, R.R., Epstein, P.R., Grimes, D.J., Hofmann, E.E., Lipp, E.K., Osterhaus, A.D., Overstreet, R.M., Porter, J.W., Smith, G.W. and Vasta, G.R. (1999) Emerging marine diseases–climate links and anthropogenic factors. Science 285, 1510

    Article  Google Scholar 

  • Hirabayashi, J. and Kasai, K. (1993) The family of metazoan metal-independent beta-galactoside -binding lectins: structure, function and molecular evolution. Glycobiology 3, 304

    Article  Google Scholar 

  • Hirashima, M., Kashio, Y., Nishi, N., Yamauchi, A., Imaizumi, T.A., Kageshita, T., Saita, N. and Nakamura, T. (2004) Galectin-9 in physiological and pathological conditions. Glycoconj J 19, 593

    Article  PubMed  Google Scholar 

  • Houzelstein, D., Goncalves, I.R., Fadden, A.J., Sidhu, S.S., Cooper, D.N.W., Drickamer, K., Leffler, H. and Poirier, F. (2004) Phylogenetic analysis of the vertebrate galectin family. Mol Biol Evol 21, 1187

    Article  CAS  Google Scholar 

  • Hsu, D.K., Hammes, S.R., Kuwabara, I., Greene, W.C. and Liu, F.T. (1996) Human T lymphotropic virus-I infection of human T lymphocytes induces expression of the beta-galactoside -binding lectin, galectin-3. Am J Pathol 148, 1670

    Google Scholar 

  • Kamhawi, S. (2006) Phlebotomine sand flies and Leishmania parasites: friends or foes? Trends Parasitol 22, 439

    Article  PubMed  Google Scholar 

  • Kamhawi, S., Ramalho-Ortigao, M., Pham, V.M., Kumar, S., Lawyer, P.G., Turco, S.J., Barillas-Mury, C., Sacks, D.L. and Valenzuela, J.G. (2004) A role for insect galectins in parasite survival. Cell 119, 329

    Article  PubMed  CAS  Google Scholar 

  • Leffler, H., Carlsson, S., Hedlund, M., Qian, Y. and Poirier, F. (2004) Introduction to galectins. Glycoconj J 19, 440

    Google Scholar 

  • Liao, D.I., Kapadia, G., Ahmed, H., Vasta, G.R. and Herzberg, O. (1994) Structure of S-lectin, a developmentally regulated vertebrate beta-galactoside -binding protein. Proc. Natl. Acad. Sci. 91, 1432

    Google Scholar 

  • Lipkowitz, M.S., Leal-Pinto, E., Cohen, B.E. and Abramson, R.G. (2004) Galectin 9 is the sugar-regulated urate transporter/channel UAT. Glycoconj J 19, 491

    Article  PubMed  Google Scholar 

  • Liu, F.-T. and Hsu, D.K. (2007) The role of galectin-3 in promotion of the inflammatory response. Drug News Perspect 20, 460

    Google Scholar 

  • Lobsanov, Y.D., Gitt, M.A., Leffler, H., Barondes, S.H. and Rini, J.M. (1993) X-ray crystal structure of the human dimeric S-Lac lectin, L-14-II, in complex with lactose at 2.9-A resolution. J Biol Chem 268, 27038

    Google Scholar 

  • Medzhitov, R. and Janeway, C.A. (2002) Decoding the patterns of self and nonself by the innate immune system. Science 296, 300

    Article  Google Scholar 

  • Mercier, S., St-Pierre, C., Pelletier, I., Ouellet, M., Tremblay, M.J. and Sato, S. (2008) Galectin-1 promotes HIV-1 infectivity in macrophages through stabilization of viral adsorption. Virology 371, 129

    Article  CAS  Google Scholar 

  • Morris, S., Ahmad, N., Andre, S., Kaltner, H., Gabius, H.-J., Brenowitz, M. and Brewer, F. (2004) Quaternary solution structures of galectins -1, -3, and -7. Glycobiology 14, 300

    Google Scholar 

  • Ogden, A.T., Nunes, I., Ko, K., Wu, S., Hines, C.S., Wang, A.F., Hegde, R.S. and Lang, R.A. (1998) GRIFIN, a novel lens-specific protein related to the galectin family. J Biol Chem 273, 28896

    Article  Google Scholar 

  • Okumura, C.Y., Baum, L.G. and Johnson, P.J. (2008) Galectin-1 on cervical epithelial cells is a receptor for the sexually transmitted human parasite Trichomonas vaginalis. Cell Microbiol 10, 2078

    Article  PubMed  CAS  Google Scholar 

  • Ouellet, M., Mercier, S., Pelletier, I., Bounou, S., Roy, J., Hirabayashi, J., Sato, S. and Tremblay, M.J. (2005) Galectin-1 acts as a soluble host factor that promotes HIV-1 infectivity through stabilization of virus attachment to host cells. J Immunol 174, 4126

    Google Scholar 

  • Pace, K.E., Lebestky, T., Hummel, T., Arnoux, P., Kwan, K. and Baum, L.G. (2002) Characterization of a novel Drosophila melanogaster galectin. Expression in developing immune, neural, and muscle tissues. J Biol Chem 277, 13091

    Article  PubMed  CAS  Google Scholar 

  • Partridge, E.A., Le Roy, C., Di Guglielmo, G.M., Pawling, J., Cheung, P., Granovsky, M., Nabi, I.R., Wrana, J.L. and Dennis, J.W. (2004) Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis. Science 306, 120

    Article  PubMed  CAS  Google Scholar 

  • Patterson, R.J., Dagher, S.F., Vyakarnam, A. and Wang, J.L. (1997) Nuclear galectins : functionally redundant components in processing of pre-mRNA. Trends Glycosci. Glycotechnol. 9, 77

    Article  CAS  Google Scholar 

  • Puche, A.C., Poirier, F., Hair, M., Bartlett, P.F. and Key, B. (1996) Role of galectin-1 in the developing mouse olfactory system. Dev Biol 179, 274

    Article  PubMed  CAS  Google Scholar 

  • Rabinovich, G.A., Liu, F.T., Hirashima, M. and Anderson, A. (2007a) An emerging role for galectins in tuning the immune response: lessons from experimental models of inflammatory disease, autoimmunity and cancer. Scand J Immunol 66, 143

    Google Scholar 

  • Rabinovich, G.A., Rubinstein, N. and Toscano, M.A. (2002) Role of galectins in inflammatory and immunomodulatory processes. Biochim Biophys Acta 1572, 274

    Article  PubMed  CAS  Google Scholar 

  • Rabinovich, G.A., Toscano, M.A., Jackson, S.S. and Vasta, G.R. (2007b) Functions of cell surface galectin-glycoprotein lattices. Curr Opin Struct Biol 17, 520

    Article  CAS  Google Scholar 

  • Rossi, B., Espeli, M., Schiff, C. and Gauthier, L. (2006) Clustering of pre-B cell integrins induces galectin-1-dependent pre-B cell receptor relocalization and activation. J Immunol 177, 796

    PubMed  CAS  Google Scholar 

  • Saouros, S., Edwards-Jones, B., Reiss, M., Sawmynaden, K., Cota, E., Simpson, P., Dowse, T.J., Jakle, U., Ramboarina, S., Shivarattan, T., Matthews, S. and Soldati-Favre, D. (2005) A novel galectin-like domain from Toxoplasma gondii micronemal protein 1 assists the folding, assembly, and transport of a cell adhesion complex. J Biol Chem 280, 38591

    Article  CAS  Google Scholar 

  • Sato, S. and Hughes, R.C. (1992) Binding specificity of a baby hamster kidney lectin for H type I and II chains, polylactosamine glycans, and appropriately glycosylated forms of laminin and fibronectin. J Biol Chem 267, 6990

    Google Scholar 

  • Sato, S. and Hughes, R.C. (1994) Regulation of secretion and surface expression of Mac-2, a galactoside -binding protein of macrophages. J Biol Chem 269, 4424

    PubMed  CAS  Google Scholar 

  • Sato, S. and Nieminen, J. (2004) Seeing strangers or announcing “danger”: Galectin-3 in two models of innate immunity Glycoconj J 19, 583

    Article  PubMed  Google Scholar 

  • Schroder, H.C., Ushijima, H., Theis, C., Seve, A.P., Hubert, J. and Muller, W.E. (1995) Expression of nuclear lectin carbohydrate-binding protein 35 in human immunodeficiency virus type 1-infected Molt-3 cells. J Acquir Immune Defic Syndr Hum Retrovirol 9, 340

    PubMed  CAS  Google Scholar 

  • Schwarz, F.P., Ahmed, H., Bianchet, M.A., Amzel, L.M. and Vasta, G.R. (1998) Thermodynamics of bovine spleen galectin-1 binding to disaccharides: correlation with structure and its effect on oligomerization at the denaturation temperature. Biochemistry 37, 5877

    Google Scholar 

  • Seetharaman, J., Kanigsberg, A., Slaaby, R., Leffler, H., Barondes, S.H. and Rini, J.M. (1998) X-ray crystal structure of the human galectin-3 carbohydrate recognition domain at 2.1-A resolution. J Biol Chem 273, 13047

    Article  PubMed  CAS  Google Scholar 

  • Shoji, H., Nishi, N., Hirashima, M. and Nakamura, T. (2003) Characterization of the Xenopus galectin family. Three structurally different types as in mammals and regulated expression during embryogenesis. J Biol Chem 278, 12293

    Article  Google Scholar 

  • Sparrow, C.P., Leffler, H. and Barondes, S.H. (1987) Multiple soluble beta-galactoside -binding lectins from human lung. J Biol Chem 262, 7390

    Google Scholar 

  • Stalz, H., Roth, U., Schleuder, D., Macht, M., Haebel, S., Strupat, K., Peter-Katalinic, J. and Hanisch, F.-G. (2006) The Geodia cydonium galectin exhibits prototype and chimera -type characteristics and a unique sequence polymorphism within its carbohydrate recognition domain. Glycobiology 16, 414

    Article  CAS  Google Scholar 

  • Stowell, S.R., Karmakar, S., Stowell, C.J., Dias-Baruffi, M., McEver, R.P. and Cummings, R.D. (2007) Human galectin-1, -2, and -4 induce surface exposure of phosphatidylserine in activated human neutrophils but not in activated T cells. Blood 109, 227

    Article  CAS  Google Scholar 

  • Stowell, S.R., Qian, Y., Karmakar, S., Koyama, N.S., Dias-Baruffi, M., Leffler, H., McEver, R.P. and Cummings, R.D. (2008) Differential roles of galectin-1 and galectin-3 in regulating leukocyte viability and cytokine secretion. J Immunol 180, 3102

    Google Scholar 

  • Tasumi, S. and Vasta, G.R. (2007) A galectin of unique domain organization from hemocytes of the Eastern oyster (Crassostrea virginica) is a receptor for the protistan parasite Perkinsus marinus. J. Immunol. 179, 3098

    Google Scholar 

  • van Die, I. and Cummings, R.D. (2010) Glycan gimmickry by parasitic helminths: a strategy for modulating the host immune response? Glycobiology 20, 2

    Article  PubMed  CAS  Google Scholar 

  • Varki, A. (2006) Nothing in glycobiology makes sense, except in the light of evolution. Cell 126, 841

    Article  PubMed  CAS  Google Scholar 

  • Vasta, G.R. (2009) Roles of galectins in infection. Nat Rev Microbiol 7, 424

    Article  PubMed  CAS  Google Scholar 

  • Vasta, G.R., Quesenberry, M., Ahmed, H. and O’Leary, N. (1999) C-type lectins and galectins mediate innate and adaptive immune functions: their roles in the complement activation pathway. Dev Comp Immunol 23, 401

    Article  PubMed  CAS  Google Scholar 

  • Walser, P.J., Kues, U., Aebi, M. and Kunzler, M. (2005) Ligand interactions of the Coprinopsis cinerea galectins . Fungal Genet Biol 42, 305

    Article  CAS  Google Scholar 

  • Watt, D.J., Jones, G.E. and Goldring, K. (2004) The involvement of galectin-1 in skeletal muscle determination, differentiation and regeneration. Glycoconj J 19, 615

    Article  PubMed  Google Scholar 

  • Yang, R.-Y., Rabinovich, G.A. and Liu, F.-T. (2008) Galectins: structure , function and therapeutic potential. Expert Rev Mol Med 10

    Google Scholar 

  • Zhou, Q. and Cummings, R.D. (1990) The S-type lectin from calf heart tissue binds selectively to the carbohydrate chains of laminin. Arch Biochem Biophys 281, 35

    Article  Google Scholar 

  • Zuñiga, E., Gruppi, A., Hirabayashi, J., Kasai, K.I. and Rabinovich, G.A. (2001) Regulated expression and effect of galectin-1 on Trypanosoma cruzi-infected macrophages: modulation of microbicidal activity and survival. Infect Immun 69, 6804

    Article  PubMed  Google Scholar 

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Acknowledgments

Research in the author’s lab reviewed here was supported by grant 5R01GM070589-06 from the National Institutes of Health, and grants IOB-0618409 and IOS0822257 from the National Science Foundation.

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  1. Department of Microbiology and Immunology, School of Medicine, IMET, University of Maryland, 21202, Baltimore, MD, USA

    Gerardo R. Vasta

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Correspondence to Gerardo R. Vasta .

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  1. Department Of Pathology Laboratory Of, Medicine, University Of Pennsylvania, Johnson Pavilion 410, Philadelphia, 19104, Pennsylvania, USA

    John D. Lambris

  2. Health Sciences Center, University of Louisville, Louisville, 40292, Kentucky, USA

    George Hajishengallis

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Vasta, G.R. (2012). Galectins as Pattern Recognition Receptors: Structure, Function, and Evolution. In: Lambris, J., Hajishengallis, G. (eds) Current Topics in Innate Immunity II. Advances in Experimental Medicine and Biology, vol 946. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0106-3_2

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