Assembly, organization and regulation of cell-surface receptors by lectin–glycan complexes

Abstract

Galectins are a family of β-galactoside-binding lectins carrying at least one consensus sequence in the carbohydrate-recognition domain. Properties of glycosylated ligands, such as N- and O-glycan branching, LacNAc (N-acetyl-lactosamine) content and the balance of α2,3- and α2,6-linked sialic acid dramatically influence galectin binding to a preferential set of counter-receptors. The presentation of specific glycans in galectin-binding partners is also critical, as proper orientation and clustering of oligosaccharide ligands on multiple carbohydrate side chains increase the binding avidity of galectins for particular glycosylated receptors. When galectins are released from the cells, they typically concentrate on the cell surface and the local matrix, raising their local concentration. Thus galectins can form their own multimers in the extracellular milieu, which in turn cross-link glycoconjugates on the cell surface generating galectin-glycan complexes that modulate intracellular signalling pathways, thus regulating cellular processes such as apoptosis, proliferation, migration and angiogenesis. Subtle changes in receptor expression, rates of protein synthesis, activities of Golgi enzymes, metabolite concentrations supporting glycan biosynthesis, density of glycans, strength of protein-protein interactions at the plasma membrane and stoichiometry may modify galectin-glycan complexes. Although galectins are key contributors to the formation of these extended glycan complexes leading to promotion of receptor segregation/clustering, and inhibition of receptor internalization by surface retention, when these complexes are disrupted, some galectins, particularly galectin-3 and -4, showed the ability to drive clathrin-independent mechanisms of endocytosis. In the present review, we summarize the data available on the assembly, hierarchical organization and regulation of conspicuous galectin-glycan complexes, and their implications in health and disease.

Multiple routes of endocytic internalization of PDGFRβ contribute to PDGF-induced STAT3 signaling

“…As galectin-3 was described to have both extra-and intra-cellular functions (Haudek et al, 2010;Elola et al, 2015) we verified whether addition of soluble recombinant galectin-3 to galectin-3-depleted cells could rescue the observed defect in PDGFRβ endocytosis. As shown in Fig.…”

Cell Surface Sialylated N-Glycan Alterations during Development

“…Galectin lattices regulate lateral mobility of integrins (34), junctional stability of N-cadherins (32), receptor distribution at the cell surface (35), turnover of endocytic receptors (33), and intracellular signaling pathways (31,(36)(37)(38). Galectins exhibit a remarkable functional diversity that participates in developmental processes, such as cell differentiation and pathophysiology, (39) cell adhesion and motility, regulation of immune homeostasis, and recognition of glycans on pathogens (26,28,40).…”

“…Galectin binding is influenced by N-glycan branching, LacNAc content and the balance of α2,3-and α2,6-linked terminal Sia (38). While Gal-1 is connected to only α2,3-sialylated poly-LacNAc, Gal-3 is connected to both α2,3-and α2,6-sialylated glycans (109).…”

Galectins in Invertebrates with a focus on <i>Caenorhabditis elegans</i>

“…Galectin has been shown to function in various biological phenomena such as development, cancer, and immunity, and Galβ1-4GlcNAc is thought to be the major endogenous recognition unit of vertebrate galectins (5)(6)(7)(8). Meanwhile, in recent years, the recognition of exogenous glycans by galectin is also thought to be important for innate immunity (3,6), and it has been shown that galectins have affinities for various disaccharide units that contain β-galactoside structure regardless of whether such disaccharides are found endogenously or exogenously (9).…”