Galectins are a family of soluble 2-galactoside-binding proteins. Several galectin types have been described (proto, chimera, and tandem-repeat), each endowed with a unique molecular structure, biochemical properties, and taxonomic distribution. Embryonic expression patterns and affinity for extracellular matrix glycoproteins have led to propose that galectins mediate developmental processes, whereas their expression in macrophages, eosinophils and basophils suggests, and their recently established recognition properties for microbes, suggest their functions in immunity. Because of its external fertilization and development, transparent embryos, short generation time, powerful genetic systems, and extensive genomic resources, the zebrafish (Danio rerio) is a useful model for in vivo studies of development and immunology. We have made substantial contributions to the biochemical, structural, and evolutionary characterization of galectins in zebrafish: we identified proto, chimera, tandem-repeat, and chimeric tandem-repeat galectins, and characterized their developmental expression and tissue distribution. We performed preliminary functional analyses: knockdown embryos for proto type galectins exhibit disrupted muscle fiber organization, retinal regeneration, and an underdeveloped heart, while chimera, tandem-repeat, and chimeric tandem-repeat galectins are up-regulated upon immune challenge. We hypothesize that (I) the proto galectins Drgal1-L2 and Drgal1-L4 play a critical role in notochord development, and are indirectly involved in myoblast differentiation and heart development through signals from the notochord or neural tube. Further, (II) the proto galectin DrGRIFIN plays an important role in eye lens development. Finally, (III) the chimeric and tandem-repeat galectins (Drgal3-L1, Drgal9-L3, and Drgal9-L4) are directly involved in innate immune responses by interacting with potential pathogens and/or by recruiting phagocytic cells to sites of acute inflammation, and/or indirectly, by interacting with receptors on their surface, inducing their activation upon infectious challenge. The proposed studies will yield (a) novel information on the biological role(s) of galectins in development and immunity in the zebrafish model;(b) novel information concerning the molecular mechanisms of cell-cell, cell-ECM, and cell-pathogen interactions that modulate embryonic development and immune functions shared between teleost fish and higher vertebrates, including man, and (c) molecular tools and resources for functional analysis of galectins in the zebrafish model that will be shared with the scientific community.
The goal of the proposed studies is to gain further insight into the biological functions of galectins (2- galactoside-binding proteins) using zebrafish (Danio rerio) as a model organism. Results will yield fundamental knowledge concerning their roles in embryonic development and immune functions in higher vertebrates, including man, and useful molecular tools/resources for the scientific community.
|Wang, Xian-Wei; Xu, Ji-Dong; Zhao, Xiao-Fan et al. (2014) A shrimp C-type lectin inhibits proliferation of the hemolymph microbiota by maintaining the expression of antimicrobial peptides. J Biol Chem 289:11779-90|
|Cammarata, Matteo; Parisi, Maria Giovanna; Benenati, Gigliola et al. (2014) A rhamnose-binding lectin from sea bass (Dicentrarchus labrax) plasma agglutinates and opsonizes pathogenic bacteria. Dev Comp Immunol 44:332-40|
|Shi, Xiu-Zhen; Wang, Lei; Xu, Sen et al. (2014) A galectin from the kuruma shrimp (Marsupenaeus japonicus) functions as an opsonin and promotes bacterial clearance from hemolymph. PLoS One 9:e91794|
|Feng, Chiguang; Ghosh, Anita; Amin, Mohammed N et al. (2013) The galectin CvGal1 from the eastern oyster (Crassostrea virginica) binds to blood group A oligosaccharides on the hemocyte surface. J Biol Chem 288:24394-409|
|Vasta, Gerardo R (2012) Galectins as pattern recognition receptors: structure, function, and evolution. Adv Exp Med Biol 946:21-36|
|Vasta, Gerardo R; Nita-Lazar, Mihai; Giomarelli, Barbara et al. (2011) Structural and functional diversity of the lectin repertoire in teleost fish: relevance to innate and adaptive immunity. Dev Comp Immunol 35:1388-99|
|Di Lella, Santiago; Sundblad, Victoria; Cerliani, Juan P et al. (2011) When galectins recognize glycans: from biochemistry to physiology and back again. Biochemistry 50:7842-57|
|Bianchet, Mario A; Odom, Eric W; Vasta, Gerardo R et al. (2010) Structure and specificity of a binary tandem domain F-lectin from striped bass (Morone saxatilis). J Mol Biol 401:239-52|
|Craig, Sonya E L; Thummel, Ryan; Ahmed, Hafiz et al. (2010) The zebrafish galectin Drgal1-l2 is expressed by proliferating Muller glia and photoreceptor progenitors and regulates the regeneration of rod photoreceptors. Invest Ophthalmol Vis Sci 51:3244-52|
|Poisa-Beiro, Laura; Dios, Sonia; Ahmed, Hafiz et al. (2009) Nodavirus infection of sea bass (Dicentrarchus labrax) induces up-regulation of galectin-1 expression with potential anti-inflammatory activity. J Immunol 183:6600-11|
Showing the most recent 10 out of 21 publications