title: The ST6Gal I sialyltransferase selectively modifies N-glycans on CD45 to negatively regulate galectin-1-induced CD45 clustering, phosphatase modulation, and T cell death.
abstract: The addition of sialic acid to T cell surface glycoproteins influences essential T cell functions such as selection in the thymus and homing in the peripheral circulation. Sialylation of glycoproteins can be regulated by expression of specific sialyltransferases that transfer sialic acid in a specific linkage to defined saccharide acceptor substrates and by expression of particular glycoproteins bearing saccharide acceptors preferentially recognized by different sialyltransferases. Addition of alpha2,6-linked sialic acid to the Galbeta1,4GlcNAc sequence, the preferred ligand for galectin-1, inhibits recognition of this saccharide ligand by galectin-1. SAalpha2,6Gal sequences, created by the ST6Gal I enzyme, are present on medullary thymocytes resistant to galectin-1-induced death but not on galectin-1-susceptible cortical thymocytes. To determine whether addition of alpha2,6-linked sialic acid to lactosamine sequences on T cell glycoproteins inhibits galectin-1 death, we expressed the ST6Gal I enzyme in a galectin-1-sensitive murine T cell line. ST6Gal I expression reduced galectin-1 binding to the cells and reduced susceptibility of the cells to galectin-1-induced cell death. Because the ST6Gal I preferentially utilizes N-glycans as acceptor substrates, we determined that N-glycans are essential for galectin-1-induced T cell death. Expression of the ST6Gal I specifically resulted in increased sialylation of N-glycans on CD45, a receptor tyrosine phosphatase that is a T cell receptor for galectin-1. ST6Gal I expression abrogated the reduction in CD45 tyrosine phosphatase activity that results from galectin-1 binding. Sialylation of CD45 by the ST6Gal I also prevented galectin-1-induced clustering of CD45 on the T cell surface, an initial step in galectin-1 cell death. Thus, regulation of glycoprotein sialylation may control susceptibility to cell death at specific points during T cell development and peripheral activation.
authors.affiliation: Department of Pathology and the Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California 90095, USA.
authors.forename: Maho
authors.initials: M
authors.lastname: Amano
authors.forename: Marisa
authors.initials: M
authors.lastname: Galvan
authors.forename: Jiale
authors.initials: J
authors.lastname: He
authors.forename: Linda G
authors.initials: LG
authors.lastname: Baum
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016923:Cell Death; D002460:Cell Line; D005434:Flow Cytometry; D037483:Galectin 1 / Q000378:metabolism*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000096:biosynthesis*; D008024:Ligands; D051379:Mice; D010957:Plasmids / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry; D011485:Protein Binding; D012799:Sialyltransferases / Q000737:chemistry* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D037483:Galectin 1; D008024:Ligands; D011134:Polysaccharides; D012799:Sialyltransferases; D017493:Leukocyte Common Antigens; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase