Journal of Biological Chemistry
Volume 285, Issue 48, 26 November 2010, Pages 37293-37301
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Glycobiology and Extracellular Matrices
HNK-1 Epitope-carrying Tenascin-C Spliced Variant Regulates the Proliferation of Mouse Embryonic Neural Stem Cells*

https://doi.org/10.1074/jbc.M110.157081Get rights and content
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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.

Development
Differentiation
Glycoconjugate
Glycoprotein
Neural Stem Cell
Tenascin
HNK-1 Antigen
Cell Signaling

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*

This work was supported, in whole or in part, by U. S. Public Health Service Grants NS11853-34 and NS26994-20. This work was also supported by a grant from the Childrens' Medical Research Foundation, Chicago, IL (to R. K. Y.), a start-up fund from Medical College of Georgia (to M. Y.), and Grant-in-aid for Young Scientists B 22790076 from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to H. Y.).

The on-line version of this article (available at http://www.jbc.org) contains supplemental Tables 1–3.

1

Supported by the Japan Society for the Japan–United States Brain Research Cooperative Program and the Naito Foundation, Japan.

2

Present address: Institute of Glycoscience, Tokai University, 1117 Kitakaname, Hiratsuka, Kanagawa 259-1292, Japan.