多结构域蛋白TCGAP对早期神经元发育调节作用的研究

发布时间：2018-11-08 11:06

【摘要】：神经元是一种有极性的细胞,其形态发生在神经系统发育过程中有着极其重要的作用。神经元形态发生的异常与很多神经系统疾病都有关。包括Rho家族GTP酶及GTP酶活化蛋白在内的很多分子都参与调节了神经元的形态发生。 TC10β/CDC42 GTP酶活化蛋白(TCGAP)是一个在发育过程中脑内特异性高表达的多结构域蛋白,已有研究表明TCGAP参与调节神经生长因子引起的PC12细胞的神经突的生长。然而其在神经系统发育过程中的作用很少被研究。在本次研究工作中,我们详细研究了TCGAP基因在神经元形态发生过程中的作用。我们的研究结果表明,在神经元形态发生过程中,TCGAP主要通过调节神经元树突的形态发生来调节神经元的形态发生。通过RNA干扰技术敲减内源性TCGAP会导致神经元树突发育的异常,主要表现在树突的长度以及分支数目的减少,在原代培养以及在体的神经元上都得到了同样的结果。由RNA干扰导致的树突减少可以很好的被TCGAP的同义突变回复。与之相对,过表达TCGAP会促进神经元树突的形成。然而无论是过表达还是敲减TCGAP对原代培养的神经元轴突发育没有显著性影响,在体内敲减TCGAP也不会影响神经元轴突的正常投射。此外,TCGAP也不参与调节脑源性神经营养因子(BDNF)引起的神经元树突的生长。我们的工作揭示了在早期神经系统发育过程中TCGAP主要是通过调节神经元树突发育来调节神经元形态发生。
[Abstract]:Neurons are polar cells whose morphology plays an extremely important role in the development of the nervous system. Neuronal morphogenesis is associated with many neurological diseases. Many molecules, including Rho family GTP enzymes and GTP enzyme activating proteins, are involved in the regulation of neuronal morphogenesis. TC10 尾 / CDC42 GTP activator protein (TCGAP) is a multidomain protein specifically expressed in the brain during development. It has been shown that TCGAP is involved in regulating the neuronal growth of PC12 cells induced by nerve growth factor (NGF). However, its role in the development of the nervous system is rarely studied. In this study, we studied the role of TCGAP gene in neuronal morphogenesis. Our results show that TCGAP regulates neuronal morphogenesis mainly by regulating neuronal dendritic morphogenesis during neuronal morphogenesis. Knockout of endogenous TCGAP by RNA interference technique can lead to abnormal dendritic development, mainly due to the decrease of dendritic length and number of branches. The same results are obtained in primary culture and in vivo neurons. Dendritic reduction caused by RNA interference can be well recovered by synonymous mutation of TCGAP. In contrast, overexpression of TCGAP promotes the formation of neuronal dendrites. However, whether overexpression or knockout TCGAP has no significant effect on axon development of primary cultured neurons, knockout TCGAP in vivo will not affect the normal projections of neuronal axons. In addition, TCGAP is not involved in regulating the dendritic growth of neurons induced by brain-derived neurotrophic factor (BDNF). Our work reveals that TCGAP regulates neuronal morphogenesis mainly by regulating neuronal dendritic development in the early stage of nervous system development.
【学位授予单位】：华东理工大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R338

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