Abstract
Galectins interact with N-acetyllactosamine (LacNAc) epitopes in transmembrane glycoproteins at the cell surface in a multivalent 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 glycoprotein 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.
Highlights
Background to the LatticeModel tose to glycoproteins at the cell surface with UDP-galactose andThe term “galectin lattice” was first used to describe the Golgi recombinant β1-4 galatosyltransferase rescued organ coloniza-N-acetylglucosaminyltransferase V (Mgat5) mutation on immune tion, suggesting that LacNAc plays a role in invasion and growth synapse formation, T cell activation and autoimmunity in mice of blood born tumor cells [25]
A number of earlier observations lead to this milestone, and generated at the cell surface and not available for further modificathe lattice model of galectin function
SE168 candidates for interactions with LacNAc, and Gal-3 model of cell surface glycoproteins regulated by galectins and N
Summary
Galectins as Adaptors: Linking Glycosylation and Metabolism with Extracellular Cues. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue R988, Toronto, Ontario, Canada M5G 1X5.
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