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翻译启动因子eIF4E和氨酸甲基化是神经元树突脊柱发育中的G3BP1功能的基础

Rui Dong¹, Xuejun Li², Angelo D Flores¹

¹Department of Neuroscience, City University of Hong Kong, Hong Kong, China.

The Journal of biological chemistry

|July 13, 2023

概括

G3BP1蛋白通过抑制蛋白质合成和与eIF4E相互作用来调节神经元发育. 氨酸甲基化控制了这种相互作用,影响了树突脊柱的形成.

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:

神经元通信依赖于树突脊柱的突触传输.
状脊柱形态对于神经元连接至关重要,但其调节不清楚.
除了应激反应之外,G3BP1蛋白在神经元发育中的作用在很大程度上是未知的.

研究的目的:

阐明G3BP1在调节树突性脊柱形态发生的机制.
为了确定神经元中G3BP1的下游目标和调节途径.
研究G3BP1在神经元发育中的作用,独立于应激反应.

主要方法:

研究了G3BP1与翻译启动因子eIF4E的相互作用.
评估了G3BP1耗尽对filopodia形成的影响.
检查了 arginine甲基化和PRMT8在G3BP1调节中的作用.
在神经元模型中利用Knockdown和修饰G3BP1的表达.

主要成果:

G3BP1通过其类似NTF2的域与eIF4E结合来抑制蛋白质合成.
G3BP1的枯竭导致filopodia的增加,通过抑制翻译启动来挽救它.
氨酸甲基化调节G3BP1-eIF4E相互作用;PRMT8倒置提升了蛋白质合成和filopodia.
甲基化模仿的G3BP1可以逆转PRMT8敲击的效果.

结论:

氨酸甲基化是树突脊柱发育过程中G3BP1的关键调节者.
eIF4E是G3BP1在神经元发育中的一个新的下游标,独立于压力.
通过翻译控制,G3BP1在平衡树突脊柱形态方面发挥着至关重要的作用.

关键词:

这是一种RNA结合蛋白.氨酸甲基化的阿尔金因.树突性脊柱树突性脊柱树突性脊柱信号传导的信号传导.突触突触是指突触中的突触.

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