PMID- 20855890 OWN - NLM STAT- MEDLINE DCOM- 20101230 LR - 20211020 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 285 IP - 48 DP - 2010 Nov 26 TI - HNK-1 epitope-carrying tenascin-C spliced variant regulates the proliferation of mouse embryonic neural stem cells. PG - 37293-301 LID - 10.1074/jbc.M110.157081 [doi] AB - 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. FAU - Yagi, Hirokazu AU - Yagi H AD - From the Institute of Molecular Medicine and Genetics and Institute of Neuroscience, Medical College of Georgia, Augusta, Georgia 30912. FAU - Yanagisawa, Makoto AU - Yanagisawa M FAU - Suzuki, Yusuke AU - Suzuki Y FAU - Nakatani, Yoshihiko AU - Nakatani Y FAU - Ariga, Toshio AU - Ariga T FAU - Kato, Koichi AU - Kato K FAU - Yu, Robert K AU - Yu RK LA - eng GR - R01 NS011853/NS/NINDS NIH HHS/United States GR - R01 NS026994/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100920 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (CD57 Antigens) RN - 0 (Epitopes) RN - 0 (Tenascin) SB - IM MH - Amino Acid Sequence MH - Animals MH - CD57 Antigens/chemistry/genetics/*metabolism MH - Cell Differentiation MH - *Cell Proliferation MH - Cells, Cultured MH - Epitopes/chemistry/genetics/*metabolism MH - Mice MH - Mice, Inbred ICR MH - Mice, Knockout MH - Molecular Sequence Data MH - Neural Stem Cells/chemistry/*cytology/metabolism MH - Protein Structure, Tertiary MH - *RNA Splicing MH - Sequence Alignment MH - Tenascin/*chemistry/genetics/*metabolism PMC - PMC2988335 EDAT- 2010/09/22 06:00 MHDA- 2010/12/31 06:00 PMCR- 2011/11/26 CRDT- 2010/09/22 06:00 PHST- 2010/09/22 06:00 [entrez] PHST- 2010/09/22 06:00 [pubmed] PHST- 2010/12/31 06:00 [medline] PHST- 2011/11/26 00:00 [pmc-release] AID - S0021-9258(20)46705-5 [pii] AID - M110.157081 [pii] AID - 10.1074/jbc.M110.157081 [doi] PST - ppublish SO - J Biol Chem. 2010 Nov 26;285(48):37293-301. doi: 10.1074/jbc.M110.157081. Epub 2010 Sep 20.