N- and O-glycans modulate galectin-1 binding, CD45 signaling, and T cell death.
Galectin-1, a beta-galactoside-binding protein highly expressed in the thymus, induces apoptosis of specific thymocyte subsets and activated T cells. Galectin-1 binds to N- and O-glycans on several glycoprotein receptors, including CD7, CD43, and CD45. Here we show that galectin-1 signaling through CD45, which carries both N- and O-glycans, is regulated by CD45 isoform expression, core 2 O-glycan formation and the balance of N-glycan sialylation. Regulation of galectin-1 T cell death by O-glycans is mediated through CD45 phosphatase activity. While galectin-1 signaling in cells expressing low molecular weight isoforms of CD45 requires expression of core 2 O-glycans (high affinity ligands for galectin-1), galectin-1 signaling in cells expressing a high molecular weight isoform of CD45 does not require core 2 O-glycans, suggesting that a larger amount of core 1 O-glycans (low affinity ligands for galectin-1) is sufficient to overcome lack of core 2 O-glycans. Furthermore, regulation of galectin-1 signaling by alpha2,6-sialylation of N-glycans is not solely dependent on CD45 phosphatase activity and can be modulated by the relative expression of enzymes that attach sialic acid in an alpha2,6- or alpha2,3-linkage. Thus, N- and O-glycans modulate galectin-1 T cell death by distinct mechanisms, and different glycosylation events can render thymocytes susceptible or resistant to galectin-1.
Earl
Lesley A
LA
Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, California 90095, USA.
Bi
Shuguang
S
Baum
Linda G
LG
D000818:Animals; D016923:Cell Death / Q000276:immunology*; D002460:Cell Line; D037483:Galectin 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006031:Glycosylation; D017493:Leukocyte Common Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D037483:Galectin 1; D011134:Polysaccharides; D014443:Tyrosine; D010744:Phosphoric Monoester Hydrolases; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; D019158:N-Acetylneuraminic Acid