Galectins as Adaptors: Linking Glycosylation and Metabolism with Extracellular Cues

Abstract

Galectins interact with N-acetyllactosamine (LacNAc) epitopes in transmembrane glycoproteins at the cell surface in a multi-valent manner forming a " lattice. " The term " galectin lattice " was first used to describe the impact of galectin-3 on immune synapse formation, T cell activation and autoimmunity (Demetriou et al. (2001) Nature 409, 733). The galectin lattice displays rapid exchange of binding partners or stochastic-binding, thereby acting as an intermediary between free diffusion of glycoproteins and stable complexes in the membrane. This includes (i) slowing diffusion and loss of receptor and transporters to coated-pit endocytosis and/ or caveolin domains, (ii) slowing the integration of transmembrane phosphatases with signaling microdomains and (iii) promoting turnover (i.e., opposing stability) of cell-cell and focal adhesion complexes. The lattice model classifies galectins as adaptors of gly-coprotein functions; regulating their localization, trafficking and thereby activity thresholds. The lattice model has been validated in immune regulation, cell adhesion and motility, and glucose homeostasis in mice. Here we review physical attributes of galectins and their N-glycan ligands and apply logical inference, coupled with convergence of biochemical, cell biology and genetic evidence that provide a strong Bayesian probability for greater utility of the lattice model.