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

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Desmosomal cadherins, desmogleins (Dsg), and desmocollins, are crucial for strong intercellular adhesion.
• Human intestinal epithelial cells specifically express the desmoglein-2 (Dsg2) isoform, a key component of desmosomes.

Purpose of the Study:

• To identify proteins associated with Dsg2 in intestinal epithelial cells.
• To elucidate the role of identified proteins in regulating Dsg2 stability and intercellular adhesion.

Main Methods:

• Proteomic screening to identify Dsg2-binding proteins.
• Biochemical assays to analyze Gal3-Dsg2 interactions and localization within lipid rafts.
• Functional assays involving Gal3 knockdown or lactose treatment to assess effects on cell adhesion.
• Analysis of Dsg2 protein internalization and degradation pathways.

Main Results:

• Proteomic analysis identified galectin-3 (Gal3) as a Dsg2-associated protein in intestinal epithelial cells.
• Gal3 binds to N-linked β-galactosides on the Dsg2 extracellular domain and co-localizes with caveolin-1 in lipid rafts.
• Down-regulation of Gal3 or inhibition of Gal3 binding with lactose significantly reduced intercellular adhesion.
• Absence of functional Gal3 led to Dsg2 internalization from the plasma membrane and subsequent proteasomal degradation.

Conclusions:

• Galectin-3 plays a novel and critical role in stabilizing desmoglein-2 at the plasma membrane.
• Gal3 is essential for maintaining intercellular adhesion in human intestinal epithelial cells.
• Disruption of the Gal3-Dsg2 interaction compromises desmosome integrity and promotes Dsg2 degradation.