Neurite differentiation is modulated in neuroblastoma cells engineered for altered acetylcholinesterase expression

C. Koenigsberger, S. Chiappa, S. Brimijoin

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Previous observations from several groups suggest that acetylcholinesterase (ACHE) may have a role in neural morphogenesis, but not solely by virtue of its ability to hydrolyze acetylcholine. We tested the possibility that AChE influences neurite outgrowth in nonenzymatic ways. With this aim, antisense oligonucleotides were used to decrease AChE levels transiently, and N1E.115 cell lines were engineered for permanently altered AChE protein expression. Cells stably transfected with a sense AChE cDNA construct increased their AChE expression 2.5-fold over the wild type and displayed significantly increased neurite outgrowth. Levels of the differentiation marker, tau, also rose. In contrast, AChE expression in cell lines containing an antisense construct was half of that observed in the wild type. Significant reductions in neurite outgrowth and tau protein accompanied this effect. Overall, these measures correlated statistically with the AChE level (p < 0.01). Furthermore, treatment of AChE-overexpressing cells with a polyclonal antibody against AChE decreased neurite outgrowth by 43%. We conclude that AChE may nave a novel noncholinergic role in neuronal differentiation.

Original languageEnglish (US)
Pages (from-to)1389-1397
Number of pages9
JournalJournal of neurochemistry
Volume69
Issue number4
DOIs
StatePublished - Oct 1997

Keywords

  • Acetylcholinesterase
  • Neurite outgrowth
  • Neuroblastoma
  • Neuronal differentiation
  • Tau protein

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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