Occludin protects secretory cells from ER stress by facilitating SNARE-dependent apical protein exocytosis
Tao Zhou, Yunzhe Lu, Chongshen Xu, Rui Wang, Liye Zhang, Pengfei Lu
Abstract
Significance Despite being the first tight junction (TJ) component discovered and numerous in vitro studies showing its TJ-related functions, Ocln has remained elusive regarding its physiological functions because Ocln null mice develop normally. Here we demonstrate that Ocln null mammary gland epithelium has intact TJ integrity, which argues against it being an essential TJ component as previously expected; rather, Ocln plays a role in regulating protein secretion by binding to SNARE components. Ocln mutant milk-producing cells exhibit defective protein secretion and augmented endoplasmic reticulum stress and unfolded protein response, ultimately leading to protein expression shutdown and lactation failure in mutant mice. Our results thus shed important light on the essential physiological functions of Ocln in the vertebrate epithelium.