帕克在Dock的下游发挥作用,以调节Drosophila中的光受体轴突引导
1Howard Hughes Medical Institute, Department of Biological Chemistry, School of Medicine, University of California, Los Angeles 90095, USA.
Cell
|July 10, 1999
概括
德罗斯菲拉p21激活激酶 (Pak) 对于指导光受体细胞轴突至关重要,作用于Dock蛋白的下游. 这项研究揭示了Pak.
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
- 发展生物学 发展生物学
背景情况:
- SH2/SH3适配蛋白 Dock 涉及从引导受体传递到 Drosophila 光受体 (R 细胞) 生长中的actin细胞骨的信号传递.
- 了解轴突引导的分子机制对于神经发育和修复至关重要.
研究的目的:
- 研究多索菲拉p21激活激酶 (Pak) 在调节R细胞轴突指导和向的Dock通路中的作用.
- 在体内阐明Dock和Pak之间的功能关系.
主要方法:
- 在R细胞轴突和生长中对Dock和Pak的同定位研究.
- 对Dock和Pak的功能丧失表型的分析.
- 对Pak的激酶活性和对Dock和Cdc42/Rac.的结合部位的评估.
- 使用带膜绑定的Pak (Pak ((myr)) 的功能的获取研究.
- 使用Pak (((myr) 的视网膜表达的码头突变动物的救援实验.
主要成果:
- 多克和帕克在R细胞轴突和生长中同位化,并进行物理相互作用.
- 在Dock和Pak的功能丧失突变导致无法区分的表型.
- 正常的R细胞连接需要Pak的激酶活性及其与Dock和Cdc42/Rac.ac.结合.
- 帕克的视网膜表达拯救了R细胞连接缺陷在码头突变.
结论:
- 德洛索菲拉Pak是R细胞轴突指导和向的关键调节者.
- 帕克作为Dock in vivo的下游效应器起作用.
- 在视觉系统中建立适当的神经连接时,Dock-Pak途径至关重要.
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