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

Mucosal Immunol. 2021 Nov;14(6):1235-1246. doi: 10.1038/s41385-021-00412-8. Epub 2021 Jun 1.

Abstract

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 1β (IRE1β), an ER-resident endonuclease and paralogue of the most evolutionarily conserved ER stress sensor IRE1α. IRE1β arose through gene duplication in early vertebrates and adopted functions unique from IRE1α which appear to underlie the basic development and physiology of mucosal tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Evolution
  • Biomarkers
  • Endoplasmic Reticulum Stress*
  • Endoribonucleases / genetics*
  • Endoribonucleases / metabolism*
  • Enzyme Activation
  • Epithelial Cells / metabolism*
  • Epithelium / physiology*
  • Gene Expression Regulation
  • Homeostasis
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mucous Membrane / physiology
  • Mucus / metabolism
  • Phylogeny
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction
  • Unfolded Protein Response

Substances

  • Biomarkers
  • Membrane Proteins
  • ERN2 protein, human
  • Protein Serine-Threonine Kinases
  • Endoribonucleases