Galectin-8 specificity to cells: from broad outside to fine inside

Glycobiology is the world of sugars: how they are made, what they look like, and what they do. Despite the importance of glycan structures in life, knowledge has been hampered due to their inherent complexity. Lectins are nature's way to decipher the intricate code held by glycans, which makes them important players in both normal and pathological physiology. A key to the understanding of lectins and their cellular effects lies in the basis of their carbohydrate specificity and the multivalent interactions occurring at a cell surface. Also in the design and synthesis of new drugs, either to be used as future tools in fruitful glycobiology experiments, or as effective therapeutics in the clinic, such information is very helpful.

This thesis is aimed at investigating the fine specificity of the two carbohydrate recognition domains of a human lectin, galectin-8, and to relate this fine specificity with cell surface binding and induced cellular effects. In short, our experiments charted the individual ligand preference displayed by the two domains, in addition to explaining how the striking monovalent affinity for sialylated ?-galactosides, shown by the N-terminal domain, was achieved. Further, we showed that although cell surface binding of intact galectin-8 didn?t require the sialic acid binding ability of the N-terminal domain, intracellular targeting following endocytosis did.