HNK-1 epitope-carrying tenascin-C spliced variant regulates the proliferation of mouse embryonic neural stem cells

Hirokazu Yagi, Makoto Yanagisawa, Yusuke Suzuki, Yoshihiko Nakatani, Toshio Ariga, Koichi Kato, Robert K Yu

Research output: Contribution to journalArticle

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Abstract

Neural stem cells (NSCs) possess high proliferative potential and the capacity for self-renewal with retention of multipotency to differentiate into neuronal and glial cells. NSCs are the source for neurogenesis during central nervous system development from fetal and adult stages. Although the human natural killer-1 (HNK-1) carbohydrate epitope is expressed predominantly in the nervous system and involved in intercellular adhesion, cell migration, and synaptic plasticity, the expression patterns and functional roles of HNK-1-containing glycoconjugates in NSCs have not been fully recognized. We found that HNK-1 was expressed in embryonic mouse NSCs and that this expression was lost during the process of differentiation. Based on proteomics analysis, it was revealed that the HNK-1 epitopes were almost exclusively displayed on an extracellular matrix protein, tenascin-C (TNC), in the mouse embryonic NSCs. Furthermore, the HNK-1 epitope was found to be present only on the largest isoform of the TNC molecules. In addition, the expression of HNK-1 was dependent on expression of the largest TNC variant but not by enzymes involved in the biosynthesis of HNK-1. By knocking down HNK-1 sulfotransferase or TNC by small interfering RNA, we further demonstrated that HNK-1 on TNC was involved in the proliferation of NSCs via modulation of the expression level of the epidermal growth factor receptor. Our finding provides insights into the function of HNK-1 carbohydrate epitopes in NSCs to maintain stemness during neural development.

Original languageEnglish (US)
Pages (from-to)37293-37301
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number48
DOIs
StatePublished - Nov 26 2010

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Tenascin
Neural Stem Cells
Stem cells
Epitopes
Neurology
Carbohydrates
Sulfotransferases
Glycoconjugates
Extracellular Matrix Proteins
Biosynthesis
Cell adhesion
Mouse Embryonic Stem Cells
Epidermal Growth Factor Receptor
Small Interfering RNA
Plasticity
Neuronal Plasticity
Protein Isoforms
Neurogenesis
Modulation
Fetal Development

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

HNK-1 epitope-carrying tenascin-C spliced variant regulates the proliferation of mouse embryonic neural stem cells. / Yagi, Hirokazu; Yanagisawa, Makoto; Suzuki, Yusuke; Nakatani, Yoshihiko; Ariga, Toshio; Kato, Koichi; Yu, Robert K.

In: Journal of Biological Chemistry, Vol. 285, No. 48, 26.11.2010, p. 37293-37301.

Research output: Contribution to journalArticle

Yagi, Hirokazu ; Yanagisawa, Makoto ; Suzuki, Yusuke ; Nakatani, Yoshihiko ; Ariga, Toshio ; Kato, Koichi ; Yu, Robert K. / HNK-1 epitope-carrying tenascin-C spliced variant regulates the proliferation of mouse embryonic neural stem cells. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 48. pp. 37293-37301.
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