Minimal role for activating transcription factor 3 in the oligodendrocyte unfolded protein response in vivo

Ramaswamy Sharma, Huiyuan Jiang, Laura Zhong, James Tseng, Alexander Gow

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

To further our goal of identifying and characterizing the functions of major components of the unfolded protein response (UPR) in oligodendrocytes, the gene encoding the activator of transcription factor 3 protein (ATF3) has been ablated in mice expressing mutant forms of the Proteolipid protein 1 (Plp1) gene and the phenotype of double mutants characterized at several levels. Mature oligodendrocytes in Plp1 mutant mice undergo UPR-induced cell stress, induce ATF3 expression and exhibit a greater propensity to die by apoptosis, which is consistent with pro-death function of ATF3 proposed from in vitro studies. However, we find that the absence of ATF3 has no effect on the levels of apoptosis in Plp1 mutants. Furthermore, we find that oligodendrocyte function appears normal in Atf3-/- mice and that motor coordination and neural communication are similarly unaffected. Accordingly, we conclude that ATF3, at best, plays a minor role in UPR signaling and its expression is more likely induced by the UPR as a secondary event in oligodendrocytes that is unrelated to cell death.

Original languageEnglish (US)
Pages (from-to)1703-1712
Number of pages10
JournalJournal of neurochemistry
Volume102
Issue number5
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

Keywords

  • Cell death
  • Endoplasmic reticulum
  • Gene ablation
  • Pelizaeus-Merzbacher disease
  • Protein misfolding
  • Unfolded protein response

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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