中国神经再生研究(英文版)

中国神经再生研究(英文版)

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

刺激微管组装可促进神经元神经突生长

  

  • 出版日期:2016-03-15 发布日期:2016-03-15

GIT1 enhances neurite outgrowth by stimulating microtubule assembly

Yi-sheng Li1, Li-xia Qin 1,  Jie Liu 1, Wei-liang Xia 1, Jian-ping Li 2, Hai-lian Shen 1,  Wei-Qiang Gao 1, 3   

  1. 1 State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Stem Cell Research Center, Ren Ji Hospital, School of Biomedical
    Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China
    2 Department of Neurology, Shanghai Renji Hospital, Shanghai, China
    3 Collarative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
  • Online:2016-03-15 Published:2016-03-15
  • Contact: Wei-Qiang Gao or Hai-lian Shen,gao.weiqiang@sjtu.edu.cn or shailian@yeah.net.

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摘要：

GIT1作为一种G蛋白偶联受体，参与神经突生长，但结论仍存在争议。我们的实验显示，GIT1在神经系统中高表达，且在大脑的整个神经突发生阶段均有所表达。在原代培养的小鼠海马神经元中，GIT1的缺失导致神经元突起和轴突样结构长度明显缩短，神经生长因子干预不能抵消这种改变。相反，GIT1过表达明显促进轴突生长，且可挽救GIT1敲除小鼠海马神经元轴突生长缺陷。从发生机制上来看，GIT1的N末端，包括ARFGAP, ANK和SHD区域足以促进轴突延伸。重要的是，实验发现GIT1与许多微管蛋白和微管相关蛋白结合，体外促进微管组装。总之，实验表明GIT1至少部分通过刺激微管组装促进神经突生长。

关键词: 神经再生, GIT1, 海马神经元, 神经突生长, 微管蛋白, 微管相关蛋白

Abstract:

 GIT1, a G-protein-coupled receptor kinase interacting protein, has been reported to be involved in neurite outgrowth. However, the neurobiological
functions of the protein remain unclear. In this study, we found that GIT1 was highly expressed in the nervous system, and its expression was maintained throughout all stages of neuritogenesis in the brain. In primary cultured mouse hippocampal neurons from GIT1 knockout mice, there was a significant reduction in total neurite length per neuron, as well as in the average length of axon-like structures,which could not be prevented by nerve growth factor treatment. Overexpression of GIT1 significantly promoted axon growth and fully rescued the axon outgrowth defect in the primary hippocampal neuron cultures from GIT1 knockout mice. The GIT1 N terminal region, including the ADP ribosylation factor-GTPase activating protein domain, the ankyrin domains and the Spa2 homology domain, were sufficient to enhance axonal extension. Importantly, GIT1 bound to many tubulin proteins and microtubule-associated proteins, and it accelerated microtubule assembly in vitro. Collectively, our findings suggest that GIT1 promotes neurite outgrowth, at least partially by stimulating microtubule assembly. This study provides new insight into the cellular and molecular pathogenesis of GIT1-associated neurological diseases.

Key words: nerve regeneration, GIT1, hippocampal neurons, neurite outgrowth, tubulin, microtubule-associated proteins, neural regeneration