Department of Pathology and Laboratory Medicine, Epithelial Pathobiology and Mucosal Inflammation Research Unit, Emory University, Atlanta, Georgia 30322.
Department of Pathology and Laboratory Medicine, Epithelial Pathobiology and Mucosal Inflammation Research Unit, Emory University, Atlanta, Georgia 30322; Department of Physiology, Biophysics and Neuroscience, CINVESTAV IPN., Av. IPN 2508, Col. San Pedro Zacatenco, 07360 Ciudad de México, Distrito Federal, México.
J Biol Chem. 2014 Apr 11;289(15):10510-10517. doi: 10.1074/jbc.M113.538538. Epub 2014 Feb 24.
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.
桥粒黏附蛋白，桥粒芯糖蛋白和桥粒胶蛋白介导细胞间的强黏附作用。人类肠道上皮细胞表达桥粒芯糖蛋白-2 同工型。肠道上皮细胞中 Dsg2 相关蛋白的蛋白质组筛选鉴定出一种凝集素，称为半乳糖凝集素-3（Gal3）。Gal3 与 Dsg2 细胞外结构域中的 N 连接β-半乳糖结合，并与脂筏中的小窝蛋白-1 共沉淀。Gal3 蛋白下调或用乳糖孵育（一种含有半乳糖的二糖，可竞争性抑制 Gal3 与 Dsg2 的结合）可降低肠道上皮细胞的细胞间黏附。在缺乏功能性 Gal3 的情况下，Dsg2 蛋白从质膜内化并在蛋白酶体中降解。这些结果表明 Gal3 在稳定肠道上皮细胞中的桥粒黏附蛋白和细胞间黏附中具有新的作用。
