The expanding roles of the Sd/Cad carbohydrate antigen and its cognate glycosyltransferase B4GALNT2 |
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Authors: | Fabio Dall'Olio Nadia Malagolini Mariella Chiricolo Marco Trinchera Anne Harduin-Lepers |
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Affiliation: | 1. Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy;2. Department of Medicine Clinical and Experimental (DMCS), University of Insubria Medical School, Varese, Italy;3. Laboratoire de Glycobiologie Structurale et Fonctionnelle, UMR CNRS 8576, Université Lille Nord de France, Lille1, 59655 Villeneuve d''Ascq, France |
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Abstract: | BackgroundThe histo-blood group antigens are carbohydrate structures present in tissues and body fluids, which contribute to the definition of the individual immunophenotype. One of these, the Sda antigen, is expressed on the surface of erythrocytes and in secretions of the vast majority of the Caucasians and other ethnic groups.Scope of reviewWe describe the multiple and unsuspected aspects of the biology of the Sda antigen and its biosynthetic enzyme β1,4-N-acetylgalactosaminyltransferase 2 (B4GALNT2) in various physiological and pathological settings.Major conclusionsThe immunodominant sugar of the Sda antigen is a β1,4-linked N-acetylgalactosamine (GalNAc). Its cognate glycosyltransferase B4GALNT2 displays a restricted pattern of tissue expression, is regulated by unknown mechanisms - including promoter methylation, and encodes at least two different proteins, one of which with an unconventionally long cytoplasmic portion. In different settings, the Sda antigen plays multiple and unsuspected roles. 1) In colon cancer, its dramatic down-regulation plays a potential role in the overexpression of sialyl Lewis antigens, increasing metastasis formation. 2) It is involved in the lytic function of murine cytotoxic T lymphocytes. 3) It prevents the development of muscular dystrophy in various dystrophic murine models, when overexpressed in muscular fibers. 4) It regulates the circulating half-life of the von Willebrand factor (vWf), determining the onset of a bleeding disorder in a murine model.General significanceThe expression of the Sda antigen has a wide impact on the physiology and the pathology of different biological systems. |
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Keywords: | aa, amino acids AchR, acetylcholine receptor B4GALNT1, β-1,4-N-acetylgalactosaminyltransferase 1 B4GALNT2, β-1,4-N-acetylgalactosaminyltransferase 2 bp, base pairs CTL, cytotoxic T lymphocytes DAPC, dystrophin-associated protein complex DBA, Dolichos biflorus agglutinin DMD, Duchenne muscular dystrophy α-DG, α-dystroglycan β-DG, β-dystroglycan Fuc, fucose Gal, galactose GalNAc, N-acetylgalactosamine Glc, glucose GlcNAc, N-acetylglucosamine GdA, glycodelin-A GdC, glycodelin-C GdF, glycodelin-F GdS, glycodelin-S HPA, Helix pomatia agglutinin Neu5Ac, N-acetylneuraminic acid Neu5Gc, N-glycolylneuraminic acid N-CAM, neural cell adhesion molecule NK, natural killer cell nt, nucleotides PHA, phytohaemagglutinin Sia, sialic acid sLea, sialyl Lewis a sLex, sialyl Lewis x THGP, Tamm&ndash Horsfall glycoprotein TLC, thin layer chromatography VVA, Vicia villosa agglutinin vWf, von Willebrand factor |
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