O-linked β-N-acetylglucosaminylation in mouse embryonic neural precursor cells

Makoto Yanagisawa, Robert K. Yu

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

In neural stem cells (NSCs), glycoconjugates and carbohydrate antigens are known not only to serve as excellent cell surface biomarkers for cellular differentiation and development but also to play important functional roles in determining cell fate. O-linked β-N-acetylglucosamine (O-GlcNAc), which modifies nuclear and cytoplasmic proteins on the serine and threonine residues, is also expected to play an important regulatory role. It is not known, however, whether O-GlcNAc is expressed in NSCs or what the function of this expression is. In this study, we evaluated the patterns and possible functions of O-GlcNAcylation in mouse embryonic neuroepithelial cells (NECs), which are known to be rich in NSCs. We confirmed the expression of O-GlcNAc transferase, O-GlcNAcase, and several O-GlcNAcylated proteins in NECs. Treatment of NECs with O-GlcNAcase inhibitors, PUGNAc and streptozotocin, induced robust accumulation of O-GlcNAc in NECs and reduction of number of NECs. In O-GlcNAcase inhibitor-treated NECs, the Rasmitogen-activated protein kinase pathway and the phosphatidylinositol 3-kinase-Akt pathway, important for proliferation and survival, respectively, were intact, but caspase-3, an executioner for cell death, was activated. These results suggest the possibility that O-GlcNAc is involved in cell death signaling in NECs. Furthermore, in NECs, we identified an O-GlcNAc-modified protein, Sp1 transcription factor. Our study is the first to evaluate expression and functions of O-GlcNAc in NECs.

Original languageEnglish (US)
Pages (from-to)3535-3545
Number of pages11
JournalJournal of Neuroscience Research
Volume87
Issue number16
DOIs
StatePublished - Dec 2009

Keywords

  • Carbohydrate
  • Development
  • Neuronal stem cell
  • Signal transduction

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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