Galectin-3 regulates desmoglein-2 and intestinal epithelial intercellular adhesion

J Biol Chem. 2014 Apr 11;289(15):10510-10517. doi: 10.1074/jbc.M113.538538. Epub 2014 Feb 24.

Abstract

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.

Keywords: Cell-Cell Interaction; Desmoglein-2; Desmosome; Galectin; Galectin-3f; Intestinal Epithelium; Protein Stability.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Communication
  • Cell Line
  • Cell Proliferation
  • Desmoglein 2 / metabolism*
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • Epithelium / metabolism
  • Galactose / chemistry
  • Galectin 3 / metabolism*
  • Gene Expression Regulation
  • Homeostasis
  • Humans
  • Intestines / cytology*
  • Lactose / chemistry
  • Membrane Microdomains / chemistry
  • Mice
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Structure, Tertiary
  • Proteomics
  • RNA, Small Interfering / metabolism
  • Recombinant Proteins / chemistry

Substances

  • Desmoglein 2
  • Galectin 3
  • RNA, Small Interfering
  • Recombinant Proteins
  • Proteasome Endopeptidase Complex
  • Lactose
  • Galactose