Protein and membrane trafficking in a dextran sulfate sodium‐induced ER stress in absorptive intestinal Caco‐2 cells

Abstract

A key morphological feature during the pathogenesis of inflammatory bowel disease (IBD) is the increased permeability of intestinal epithelial cells. Here, we address the implication of ER stress in protein and membrane trafficking in a dextran sulfate sodium (DSS)‐induced IBD‐like phenotype of absorptive intestinal Caco‐2 cells. We show that DSS treatment significantly reduces the transepithelial electric resistance (TEER) of Caco‐2 cells, while keeping the cell viability intact. The altered cell polarity is associated with an increase in the expression levels of the ER stress protein markers, BiP, CHOP, ATF4 and XBP1 as well as an impaired intracellular trafficking and polarized sorting of sucrase‐isomaltase (SI). SI associates normally with lipid rafts and the impaired sorting in DSS‐treated cells is likely due to reduced cholesterol levels and subsequent distortion of the lipid rafts. We conclude that perturbation of ER homeostasis in DSS‐treated Caco‐2 cells impairs membrane and protein trafficking resulting in altered cellular integrity.