通过分泌的proneurotrophins调节细胞存活率
1Division of Hematology, Department of Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Science (New York, N.Y.)
|December 1, 2001
概括
亲神经营养素,如亲神经生长因子 (NGF) 和亲大脑衍生神经营养因子 (BDNF),通过细胞外分泌和分裂. 这些前型激活p75神经热素受体 (p75NTR) 诱导亡,与促进生存的成熟形式不同.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 神经营养素是调节神经元生存,分化和细胞死亡的关键生长因子.
- 神经营养素被合成为不活跃的前型,通常在细胞内分裂,产生成熟的,分泌的连接体.
- 主要认为proneurotrophins的生物作用是不活跃的前体.
研究的目的:
- 为了研究proneurotrophins的细胞外裂变和生物活性.
- 为了确定参与proneurotrophin处理的特定蛋白酶.
- 阐明由前神经和成熟神经激活的差异信号通路.
主要方法:
- 培养的神经元被用来研究proforms和成熟的神经营养素的影响.
- 分析了亲神经生长因子 (NGF) 和亲大脑衍生神经营养因子 (BDNF) 的细胞外分裂.
- 评估了血清蛋白酶等离子体和矩阵金属蛋白酶 (MMP) 在裂变中的参与.
- 对p75神经质蛋白受体 (p75NTR) 和TrkA受体进行了联结受体结合测定和细胞信号分析.
主要成果:
- ProNGF和proBDNF是由等离子体和特定的MMPs在细胞外分泌和分裂.
- NGF与p75NTR.高亲和力结合在一起.
- 与p75NTR结合的ProNGF会在培养的神经元中诱导亡,而TrkA介导的生存或差异化的激活最小.
- 成熟的神经热素形式优先激活Trk受体以促进生存.
结论:
- 蛋白质分解裂变是神经特洛芬生物作用的关键调节机制.
- 神经营养素的前型通过p75NTR优先发出信号以调解亡.
- 成熟的神经特洛芬通过Trk受体发出信号,促进神经元的生存和分化.
- 这种差异信号突出显示了一种新的神经营蛋白介导细胞调节层.
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