Galectin-3 Regulates Desmoglein-2 and Intestinal Epithelial Intercellular Adhesion*

Background: Desmoglein-2 mediates intestinal epithelial intercellular adhesion. Results: Galectin-3 was identified to associate with the ectodomain of desmoglein-2 and inhibit the degradation of desmoglein-2 and enhance intercellular adhesion. Conclusion: Galectin-3 lattices stabilize desmoglein-2 at the cell surface to regulate intercellular adhesion in intestinal epithelial cells. Significance: This study identifies a novel role of galectin-3 in controlling desmosome structure and function. The desmosomal cadherins, desmogleins, and desmocollins mediate strong intercellular adhesion. Human intestinal epithelial cells express the desmoglein-2 isoform. A proteomic screen for Dsg2-associated proteins in intestinal epithelial cells identified a lectin referred to as galectin-3 (Gal3). Gal3 bound to N-linked β-galactosides in Dsg2 extracellular domain and co-sedimented with caveolin-1 in lipid rafts. Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. In the absence of functional Gal3, Dsg2 protein was internalized from the plasma membrane and degraded in the proteasome. These results report a novel role of Gal3 in stabilizing a desmosomal cadherin and intercellular adhesion in intestinal epithelial cells.

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