Functions of cell surface galectin-glycoprotein lattices

Abstract

Programmed remodeling of cell surface glycans by the sequential action of specific glycosyltransferases can control biological processes by generating or masking ligands for endogenous lectins. Galectins, a family of animal lectins with affinity for beta-galactosides, can form multivalent complexes with cell surface glycoconjugates and deliver a variety of intracellular signals to modulate cell activation, differentiation, and survival. Recent efforts involving genetic or biochemical manipulation of O-glycosylation and N-glycosylation pathways, as well as blockade of the synthesis of endogenous galectins, have illuminated essential roles for galectin-glycoprotein lattices in the control of biological processes including receptor turnover and endocytosis, host-pathogen interactions, and immune cell activation and homeostasis.

Figure 1. Biochemistry and functional relevance of galectin-glycoprotein lattices

(A) Schematic representation of the structure of different monomeric and oligomeric members of the galectin family. Proto-type galectins contain one CRD and exist in solution as homodimers. Chimera-type galectins are thought to undergo a conformational change following carbohydrate ligand binding which enables their oligomerization as pentamers. Tandem-repeat type galectins contain two distinct CRDs in tandem, connected by a linker of up to 70 amino acids, and are thus inherently dimeric. (B) Schematic representation of lattice formation between multivalent galectins and multivalent carbohydrate ligands. (C) Biological relevance of galectin-glycoprotein lattices.

Figure 2. Galectin-glycoprotein lattices in the regulation of receptor turnover, cell signaling and survival

(A) The degree of N-glycan branching controls galectin-glycoprotein lattice formation, which in turn modulates receptor turnover and signaling. (B) Differential sialylation of cell surface glycoproteins selectively influences the formation of galectin-glycoprotein lattices in distinct T-helper cells, thus regulating their susceptibility to galectin-1-induced cell death.