Recognition of sulfated hexosamine upon construction of the nervous system

神经系统构建过程中硫酸化己糖胺的识别

• 批准号: 14082202
• 负责人: MURAMATSU Takashi
• 金额: $ 56.45万
• 依托单位: Aichi Gakuin University (2004-2006)Nagoya University (2002-2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14082202/
• 关键词: Sulfotransferse; Proteoglycan; Neurogenesis; Auditory deficits; Brain injury; Keratan sulfate; Knockout mice; Midkine; ニューログリカンC; 神経前駆体細胞; プレイオトロフィン; トランスジェニックマウス; スルホトランスフェラーゼ; ヘパラン硫酸; N-アセチルグルコミン; 神経幹細胞; IGnT; セレクチン; リンパ球ホーミング; パイエル板

We generated mice deficient in N-acetylglucosamine 6-sulfotransferase-1 (GlcNAc6ST-1). These mice exhibited lower activity in lymphocyte homing to lymph nodes compared to wild-type mice, establishing that GlcNAc6ST-1 is involved in synthesis of L-selectin ligand. International collaboration yielded double knockout mice deficient in both GlcNAc6ST-1 and -2. Studies using the double knockout mice revealed that GlcNAc&ST-1 and -2 co-operate in production of L-selectin ligand. GlcNAc6ST-1 was also involved in synthesis of keratan sulfate. Glia scar formation upon brain injury was reduced in GlcNAc6ST-1 knockout mice, indicating that keratan sulfate hinders repair of injured brain through promotion of glia scar formation. Midkine is a heparin-binding growth factor, which promotes growth, survival and migration of target cells. Mice doubly deficient in both midkine and pleiotrophin, another member of the growth factor family, exhibited auditory deficits and female infertility, and was reduced in spontaneous locomotive activity. Using neural precursor cells derived from midkine-deficient mice, we found that midkine promotes growth and survival of neural precursor cells without affecting their differentiation capability. These activities are the basis of promotion of neurogenesis by midkine. The glycosaminoglycan structure required for strong binding to midkine was clarified to be repeated structures composed of chondroitin sulfate E units or heparan sulfate trisulfated units. As midkine receptors, proteoglycans, integrins and low density lipoprotein receptor-related proteins are important, and were proposed to form molecular complex in the presence of midkine. Upon process formation of oligodendrocyte precursor-like cells, neuroglycan C, a part time proteoglycan was also identified as a component of the receptor.

我们产生了缺乏N-乙酰葡萄糖6-硫代转移酶1（GlcNAC6ST-1）的小鼠。与野生型小鼠相比，这些小鼠在淋巴结淋巴结中的活性较低，并确定GlcNAC6ST-1参与L-甲基蛋白配体的合成。国际合作产生了双敲除小鼠在GLCNAC6ST -1和-2中的缺陷。使用双基因敲除小鼠进行的研究表明，L-选择蛋白配体的生产中GlcNAC＆ST-1和-2合作。 GlcNAC6ST-1也参与了硫酸角酯的合成。 GLCNAC6ST-1敲除小鼠中脑损伤后的胶质疤痕形成，这表明硫酸角酸硫酸盐通过促进神经胶质疤痕形成而阻碍受伤的脑修复。 Midkine是一种肝素结合生长因子，可促进靶细胞的生长，存活和迁移。生长因子家族的另一位成员中金和pleiotiotrophin双重缺乏，表现出听觉缺陷和女性不孕症，并且在自发的机车活性中降低了。使用源自中心缺陷型小鼠的神经前体细胞，我们发现中系可促进神经前体细胞的生长和存活，而不会影响其分化能力。这些活性是促进神经发生的基础。阐明了与中酮的强结合所需的糖胺聚糖结构，以重复由硫酸软骨素E单元或硫酸乙酰肝素三硫酸盐单位组成的重复结构。由于中胺受体，蛋白聚糖，整合素和低密度脂蛋白受体相关蛋白很重要，并提出在中菌存在下形成分子络合物。在形成少突胶质前体样细胞的过程后，神经聚糖C，兼职蛋白聚糖也被鉴定为受体的成分。

项目成果

α4β1- and α61-integrins are functional receptors for midkine, a heparin-binding growth factor

α4β1- 和 α61- 整合素是中期因子（一种肝素结合生长因子）的功能性受体

• 发表时间: 2004
• 期刊: J. Cell Sci 111
• 作者: Muramatsu;H.;et al.
• 通讯作者: et al.

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