Galectin-1 interactions with N- and O-glycans are dependent on physical characteristics of galectin linkers and presentation of glycan ligands.

摘要

The galectin family of beta-galactoside binding proteins is involved in diverse regulatory pathways of the immune system. Galectin-1, a homodimeric prototype galectin, and galectin-9, a tandem repeat type galectin, are both expressed in the thymus and induce apoptosis of thymocytes. Because of the differences in structure between galectin-1 and galectin-9, the mechanisms of glycan recognition by galectin-1 and galectin-9 are distinct. In this work, I have investigated the aspects of galectin and glycan structure that have roles in regulating the galectin-glycan interface.;Galectin recognition of glycans is dependent upon the abundance, structure, and presentation of glycans on glycoprotein backbones, and on the structure, orientation, and presentation of galectin carbohydrate recognition domains (CRDs). I have investigated the role of both N- and O-glycans on CD45 in regulating galectin-1 T cell death, and have found that galectin signaling through glycoprotein receptors is dependent upon both the type of glycan expressed on the glycoprotein, as well as on the relative abundance of glycans. I have also investigated the role of galectin structure on signaling pathway and potency, and have found that while the specific glycoprotein receptor bound and the signaling events initiated are dependent upon the glycan specificity of the galectin CRD, the potency and effective galectin signaling concentration are dependent upon the presentation of galectin CRDs. Together, my results indicate that signaling through the glycan-galectin interface is a complex process, and is dependent on a variety of structural factors of both glycans and galectins.