Galectin History, Some Stories, and Some Outstanding Questions

Abstract

The proteins now called galectins were discovered about 1975 based on their galactoside-binding activity, in a quest to find proteins that decode complex cell-surface glycans, to take part in cell adhesion. They were defined and named in 1994 based on conserved β-galactoside binding sites found within their characteristic ~130 amino acid (aa) carbohydrate recognition domains (CRDs). However, already at their initial discovery, it was also realized that galectins reside in the cytosol or nucleus for much of their life time, and reach their galactoside ligands only after non-classical secretion that bypasses the Golgi apparatus. Here some of the early studies (mainly before 1994) will be summarized, and exemplified with some galectin stories. The phylogenetic relationships of vertebrate galectins will be summarized as a background. The galectin field has developed rapidly after 1994 in many directions. A few basic outstanding questions will be raised and briefly discussed. What determines galectin binding affinity and specificity for natural glycoconjugate ligands? What is the functional role of galectin fine specificity for carbohydrates? Is there a functional connection between on one hand the cytosolic and nuclear galectin functions and on the other extracellular/intravesicular activities? Are there regulatory loops?