为RPTPσ聚类和神经元扩展提供蛋白质甘氨酸特异性的分子开关
Charlotte H Coles1, Yingjie Shen, Alan P Tenney
1Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
概括
肝和胆固醇硫酸蛋白质糖 (HSPGs和CSPGs) 对通过受体蛋白氨酸酸酶sigma (RPTPσ) 的感觉神经元延伸有相反的影响. RPTPσ通过CSPGs进行抑制,通过HSPGs进行促进,揭示了一个新的监管机制.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 肝和胆素硫酸盐蛋白质糖 (HSPG和CSPG) 调节细胞表面信号,具有相反的效果.
- 丁硫酸盐蛋白质糖 (CSPGs) 是通过受体蛋白氨酸酸酶sigma (RPTPσ) 的神经再生的已知抑制剂.
研究的目的:
- 为了研究RPTPσ在感觉神经元扩展中的双重作用.
- 阐明RPTPσ调解HSPG和CSPG对立作用的机制.
主要方法:
- 对RPTPσ结合部位的晶体分析.
- 测量RPTPσectodomain寡合化的生物化学试验.
- 免疫光显微镜以确定RPTPσ和蛋白质糖的细胞局部.
主要成果:
- RPTPσ表现出形态可塑性,可以容纳具有相似亲和力的HSPG和CSPG.
- 肝素硫酸盐 (HS) 诱导了RPTPσ外域寡合化,而胆固醇硫酸盐 (CS) 则抑制了它.
- RPTPσ和HSPG在感官神经元点上同位,而CSPG在细胞外基质中.
结论:
- RPTPσ在感觉神经元延伸中以双模式作用,介导CSPG诱导的抑制和HSPG诱导的增长促进.
- 蛋白质甘氨酸在控制RPTPσ寡合化方面竞争,从而对神经元扩展产生相反的影响.
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