Structural information encoded in complex carbohydrates mediates interactions between cells, or between cells and the extracellular matrix (ECM). The information is decoded by highly specific carbohydrate-binding receptors including lectins. One such family of beta-galactoside-binding lectins, the galectins, are synthesized in the cytosol and released into the extracellular space. Unique expression patterns, tissue distribution, and their affinity for endogenous ligands (ECM glycoproteins) and exogenous ligands (bacterial pathogens) have led to propose that galectins are involved in multiple functions. However, their biological roles are yet to be unequivocally established in vivo, due in part to the highly diversified (and functionally redundant"""""""") galectin repertoire of mammalian models. Zebrafish is a model of choice for these studies because it offers advantages over mammalian models, such as external fertilization, a short development period, transparent embryos, a large collection of mutants, and, based on our preliminary results, a less diversified galectin repertoire. We have partially characterized selected zebrafish galectins, developed a useful suite of molecular tools, and initiated studies aimed at elucidating their biological roles. By a """"""""loss-of-function"""""""" approach targeted to a zebrafish galectin, which is a homologue of the mammalian galectin-1 and displays a unique expression pattern, we identified a tentative phenotype with a defect in muscle cell organization. We propose that: (a) galectins play a critical role in tissue development and organization, possibly by mediating cell migration and adhesion, and are indirectly involved in cell differentiation; and (b) galectins are involved in inflammation by interacting directly with potential pathogens and/or recruiting phagocytic cells (macrophages and neutrophils) to the infection sites. To test these hypotheses we will specifically: (a) complete the molecular characterization of the zebrafish galectin repertoire, including the identification of their ligands, and their patterns of spatial and temporal expression; (b) experimentally modulate/disrupt galectin function to assess their biological roles. Expected benefits include novel molecular tools and resources (available through the Consortium for Functional Glycomics) for functional analysis of galectins, and novel information on their interactions with cells, ECM and pathogens, that modulate their multiple functions in vertebrates.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM070589-01
Application #
6758255
Study Section
Special Emphasis Panel (ZRG1-DEV-1 (90))
Program Officer
Marino, Pamela
Project Start
2004-09-20
Project End
2008-08-31
Budget Start
2004-09-20
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$207,900
Indirect Cost
Name
University of MD Biotechnology Institute
Department
Type
Organized Research Units
DUNS #
603819210
City
Baltimore
State
MD
Country
United States
Zip Code
21202
Vasta, Gerardo R; Feng, Chiguang; González-Montalbán, Nuria et al. (2017) Functions of galectins as 'self/non-self'-recognition and effector factors. Pathog Dis 75:
Nita-Lazar, Mihai; Mancini, Justin; Feng, Chiguang et al. (2016) The zebrafish galectins Drgal1-L2 and Drgal3-L1 bind in vitro to the infectious hematopoietic necrosis virus (IHNV) glycoprotein and reduce viral adhesion to fish epithelial cells. Dev Comp Immunol 55:241-252
Feng, Chiguang; Ghosh, Anita; Amin, Mohammed N et al. (2015) Galectin CvGal2 from the Eastern Oyster (Crassostrea virginica) Displays Unique Specificity for ABH Blood Group Oligosaccharides and Differentially Recognizes Sympatric Perkinsus Species. Biochemistry 54:4711-30
Nita-Lazar, Mihai; Banerjee, Aditi; Feng, Chiguang et al. (2015) Galectins regulate the inflammatory response in airway epithelial cells exposed to microbial neuraminidase by modulating the expression of SOCS1 and RIG1. Mol Immunol 68:194-202
Vasta, G R; Feng, C; Bianchet, M A et al. (2015) Structural, functional, and evolutionary aspects of galectins in aquatic mollusks: From a sweet tooth to the Trojan horse. Fish Shellfish Immunol 46:94-106
Nita-Lazar, Mihai; Banerjee, Aditi; Feng, Chiguang et al. (2015) Desialylation of airway epithelial cells during influenza virus infection enhances pneumococcal adhesion via galectin binding. Mol Immunol 65:1-16
Feng, Chiguang; Nita-Lazar, Mihai; González-Montalbán, Nuria et al. (2015) Manipulating galectin expression in zebrafish (Danio rerio). Methods Mol Biol 1207:327-41
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
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

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