Deficiency of suppressor enhancer Lin12 1 like (SEL1L) in mice leads to systemic endoplasmic reticulum stress and embryonic lethality

Adam B. Francisco, Rajni Singh, Shuai Li, Anish K. Vani, Liu Yang, Robert J. Munroe, Giuseppe Diaferia, Marina Cardano, Ida Biunno, Ling Qi, John C. Schimenti, Qiaoming Long

Research output: Contribution to journalArticle

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Abstract

Stress in the endoplasmic reticulum (ER) plays an important causal role in the pathogenesis of several chronic diseases such as Alzheimer, Parkinson, and diabetes mellitus. Insight into the genetic determinants responsible for ER homeostasis will greatly facilitate the development of therapeutic strategies for the treatment of these debilitating diseases. Suppressor enhancer Lin12 1 like (SEL1L) is an ER membrane protein and was thought to be involved in the quality control of secreted proteins. Here we show that the mice homozygous mutant for SEL1L were embryonic lethal. Electron microscopy studies revealed a severely dilated ER in the fetal liver of mutant embryos, indicative of alteration in ER homeostasis. Consistent with this, several ER stress responsive genes were significantly up-regulated in the mutant embryos. Mouse embryonic fibroblast cells deficient in SEL1L exhibited activated unfolded protein response at the basal state, impaired ER-associated protein degradation, and reduced protein secretion. Furthermore, markedly increased apoptosis was observed in the forebrain and dorsal root ganglions of mutant embryos. Taken together, our results demonstrate an essential role for SEL1L in protein quality control during mouse embryonic development.

Original languageEnglish
Pages (from-to)13694-13703
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number18
DOIs
Publication statusPublished - Apr 30 2010

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Endoplasmic Reticulum Stress
Endoplasmic Reticulum
Embryonic Structures
Quality Control
Proteins
Homeostasis
Endoplasmic Reticulum-Associated Degradation
Quality control
Unfolded Protein Response
Spinal Ganglia
Prosencephalon
Proteolysis
Embryonic Development
Fibroblasts
Electron Microscopy
Diabetes Mellitus
Medical problems
Membrane Proteins
Chronic Disease
Liver

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Deficiency of suppressor enhancer Lin12 1 like (SEL1L) in mice leads to systemic endoplasmic reticulum stress and embryonic lethality. / Francisco, Adam B.; Singh, Rajni; Li, Shuai; Vani, Anish K.; Yang, Liu; Munroe, Robert J.; Diaferia, Giuseppe; Cardano, Marina; Biunno, Ida; Qi, Ling; Schimenti, John C.; Long, Qiaoming.

In: Journal of Biological Chemistry, Vol. 285, No. 18, 30.04.2010, p. 13694-13703.

Research output: Contribution to journalArticle

Francisco, AB, Singh, R, Li, S, Vani, AK, Yang, L, Munroe, RJ, Diaferia, G, Cardano, M, Biunno, I, Qi, L, Schimenti, JC & Long, Q 2010, 'Deficiency of suppressor enhancer Lin12 1 like (SEL1L) in mice leads to systemic endoplasmic reticulum stress and embryonic lethality', Journal of Biological Chemistry, vol. 285, no. 18, pp. 13694-13703. https://doi.org/10.1074/jbc.M109.085340
Francisco, Adam B. ; Singh, Rajni ; Li, Shuai ; Vani, Anish K. ; Yang, Liu ; Munroe, Robert J. ; Diaferia, Giuseppe ; Cardano, Marina ; Biunno, Ida ; Qi, Ling ; Schimenti, John C. ; Long, Qiaoming. / Deficiency of suppressor enhancer Lin12 1 like (SEL1L) in mice leads to systemic endoplasmic reticulum stress and embryonic lethality. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 18. pp. 13694-13703.
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