Negative feedback by IRE1ß optimizes mucin production in goblet cells.
Proc Natl Acad Sci U S A
; 110(8): 2864-9, 2013 Feb 19.
Article
en En
| MEDLINE
| ID: mdl-23386727
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, IRE1ß is expressed selectively in the digestive tract, and its function remains unclear. Here, we report that IRE1ß plays a distinctive role in mucin-secreting goblet cells. In IRE1ß(-/-) 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 IRE1ß(-/-) mice. These findings suggest that in goblet cells, IRE1ß, but not IRE1α, promotes efficient protein folding and secretion in the ER by optimizing the level of mRNA encoding their major secretory product, MUC2.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Serina-Treonina Quinasas
/
Células Caliciformes
/
Mucina 2
/
Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2013
Tipo del documento:
Article
País de afiliación:
Japón