Evolution and function of the epithelial cell-specific ER stress sensor IRE1β

Barrier epithelial cells lining the mucosal surfaces of the gastrointestinal and respiratory tracts interface directly with the environment. As such, these tissues are continuously challenged to maintain a healthy equilibrium between immunity and tolerance against environmental toxins, food components, and microbes. An extracellular mucus barrier, produced and secreted by the underlying epithelium plays a central role in this host defense response. Several dedicated molecules with a unique tissue-specific expression in mucosal epithelia govern mucosal homeostasis. Here, we review the biology of Inositol-requiring enzyme 1 beta (IRE1 beta), an ER-resident endonuclease and paralogue of the most evolutionarily conserved ER stress sensor IRE1 alpha. IRE1 beta arose through gene duplication in early vertebrates and adopted functions unique from IRE1 alpha which appear to underlie the basic development and physiology of mucosal tissues.

Automated summary

Barrier epithelial cells lining mucosal surfaces in the gastrointestinal and respiratory tracts play a crucial role in maintaining the balance between immunity and tolerance against environmental challenges. The extracellular mucus barrier produced by these cells is central to host defense. Molecules like IRE1 beta regulate mucosal homeostasis, with unique functions distinct from IRE1 alpha.