用于GDNF的功能性受体被c-ret proto-oncogene编码
M Trupp1, E Arenas, M Fainzilber
1Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Nature
|June 27, 1996
概括
质细胞系衍生的中毒因子 (GDNF) 与Ret受体氨酸激酶结合,调解神经营养效应. 这确定了Ret作为一个功能性的GDNF受体,对运动和多巴胺基神经元的存活至关重要.
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:
- 质细胞系衍生中性因素 (GDNF) 支持各种神经元的存活,包括多巴胺和运动神经元.
- 尽管它具有神经营养作用,但GDNF受体仍然未被确定.
- GDNF与TGF-β超级家族具有结构上的相似之处,这表明它是一种受体系统.
研究的目的:
- 为了确定Glial细胞系衍生中性因子 (GDNF) 的功能受体.
- 为了研究c-ret原型瘤基因产品在调解GDNF的神经营养效应中的作用.
主要方法:
- 使用GDNF响应的运动神经元细胞系进行结合试验和氨酸酸化研究.
- 用Ret感染原始纤维细胞以评估GDNF介导反应.
- 对成年黑质体中c-ret mRNA表达的分析以及GDNF对Ret阳性神经元的保护作用.
主要成果:
- GDNF直接结合并诱导Ret原型瘤基因产品的氨酸酸化,这是一个受体氨酸激酶.
- 当在天真细胞中表达时,Ret调解GDNF诱导的生存和生长信号.
- c-ret mRNA在多巴胺基神经元中高度表达,GDNF保护这些Ret阳性神经元免受细胞死亡.
结论:
- 这种c-ret原型瘤基因产物作为GDNF受体起作用.
- 雷特调解了GDNF对运动神经元和多巴胺基神经元的神经营养效应.
- 这一发现为了解和潜在地治疗影响这些神经元群体的神经退行性疾病提供了一个分子标.
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