Galectin-3 alters the lateral mobility and clustering of β1-integrin receptors

Abstract

Glycoprotein receptors are influenced by myriad intermolecular interactions at the cell surface. Specific glycan structures may interact with endogenous lectins that enforce or disrupt receptor-receptor interactions. Glycoproteins bound by multivalent lectins may form extended oligomers or lattices, altering the lateral mobility of the receptor and influencing its function through endocytosis or changes in activation. In this study, we have examined the interaction of Galectin-3 (Gal-3), a human lectin, with adhesion receptors. We measured the effect of recombinant Gal-3 added exogenously on the lateral mobility of the α5β1 integrin on HeLa cells. Using single-particle tracking (SPT) we detected increased lateral mobility of the integrin in the presence of Gal-3, while its truncated C-terminal domain (Gal-3C) showed only minor reductions in lateral mobility. Treatment of cells with Gal-3 increased β1-integrin mediated migration with no apparent changes in viability. In contrast, Gal-3C decreased both cell migration and viability. Fluorescence microscopy allowed us to confirm that exogenous Gal-3 resulted in reorganization of the integrin into larger clusters. We used a proteomics analysis to confirm that cells expressed endogenous Gal-3, and found that addition of competitive oligosaccharide ligands for the lectin altered the lateral mobility of the integrin. Together, our results are consistent with a Gal-3–integrin lattice model of binding and confirm that the lateral mobility of integrins is natively regulated, in part, by galectins.

Galectin-3 modulates the polarized surface delivery of β1-integrin in epithelial cells

“…Integrins function as αβ-heterodimeric receptors to convey polarity cues from the extracellular matrix (Yu et al, 2005) and it has been previously demonstrated that β1-integrins are not exclusively localized on the basolateral surface but are also located on the apical surface of subconfluent and fully polarized MDCK cells (Praetorius and Spring, 2002;Schwimmer and Ojakian, 1995;Zuk and Matlin, 1996). We found that galectin-3 interacts with α2β1-integrin at the apical membrane domain of MDCK cells.…”

“…Moreover, endogenous or externally supplied galectin-3 sorts newly synthesized as well as internalized β1-integrin to the apical cell surface. The question of whether β1-integrin can be redistributed to the apical cell surface by extracellular interaction partners has been addressed previously (Zuk and Matlin, 1996). Apical overlay of MDCK cells with the extracellular matrix component type I collagen did not stimulate delivery of additional newly synthesized integrin to apical plasma membranes.…”

“…Apical overlay of MDCK cells with the extracellular matrix component type I collagen did not stimulate delivery of additional newly synthesized integrin to apical plasma membranes. However, interaction of β1-integrin with collagen on the apical membrane drives the formation of tubulocysts (Zuk and Matlin, 1996). Evidence for a link between tubulogenesis and galectin-3 expression originally came from Bao and Hughes (1995).…”

Galectin‐3 and risk of atrial fibrillation: A systematic review and meta‐analysis

“…Galectin‐3 was originally discovered in 1982 as Mac‐2, cloned in 1991, and subsequently recognized as a β‐galactoside‐binding lectin . It has diverse biological functions such as regulation of cell adhesion, immunity, inflammation, and fibrosis . Its pathological role in the heart, specifically heart failure, has been discussed in detail by the excellent review here .…”

β4-Integrin/PI3K Signaling Promotes Tumor Progression through the Galectin-3–N-Glycan Complex

“…Galectin-3 has a high affinity for b1,6GlcNAc-branched Nglycans modified by polylactosamine consisting of b-galactoside sugars. The oligomerization of integrins by galectin-3-mediated cross-linking between the b1,6GlcNAc-branched N-glycans on integrins promotes integrin function (25,27,32). To understand why deletion of N-glycosylation suppressed the ability of b4integrin to promote cancer cell progression, we examined the relationship between galectin-3 binding to b4-integrin and cellular functions of b4-integrin.…”