title: Negative feedback by IRE1β optimizes mucin production in goblet cells.
abstract: In mammals, the prototypical endoplasmic reticulum (ER) stress sensor inositol-requiring enzyme 1 (IRE1) has diverged into two paralogs. IRE1α is broadly expressed and mediates the unconventional splicing of X-box binding protein 1 (XBP1) mRNA during ER stress. By contrast, IRE1β is expressed selectively in the digestive tract, and its function remains unclear. Here, we report that IRE1β plays a distinctive role in mucin-secreting goblet cells. In IRE1β(-/-) mice, aberrant mucin 2 (MUC2) accumulated in the ER of goblet cells, accompanied by ER distension and elevated ER stress signaling such as increased XBP1 mRNA splicing. In contrast, conditional IRE1α(-/-) mice showed no such ER distension but a marked decrease in spliced XBP1 mRNA. mRNA stability assay revealed that MUC2 mRNA was greatly stabilized in IRE1β(-/-) mice. These findings suggest that in goblet cells, IRE1β, but not IRE1α, promotes efficient protein folding and secretion in the ER by optimizing the level of mRNA encoding their major secretory product, MUC2.
authors: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara 630-0192, Japan. atsuru@gtc.naist.jp
authors: Akio
authors: A
authors: Tsuru
authors: Naoko
authors: N
authors: Fujimoto
authors: Satsuki
authors: S
authors: Takahashi
authors: Michiko
authors: M
authors: Saito
authors: Daisuke
authors: D
authors: Nakamura
authors: Megumi
authors: M
authors: Iwano
authors: Takao
authors: T
authors: Iwawaki
authors: Hiroshi
authors: H
authors: Kadokura
authors: David
authors: D
authors: Ron
authors: Kenji
authors: K
authors: Kohno
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020397:Goblet Cells / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D055262:Mucin-2 / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D055262:Mucin-2; D012333:RNA, Messenger; C486556:Ern2 protein, mouse; D017346:Protein Serine-Threonine Kinases
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