E3 泛基因酶TRIM9 调节突触功能和动因动态,以应对网林-1 的作用
Laura E McCormick1, Elliot B Evans1, Natalie K Barker2,3
1Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Molecular biology of the cell
|March 20, 2024
概括
E3 泛素酶TRIM9 调节树突性脊柱的发育和功能. TRIM9对于对网氨酸的突触反应至关重要,控制细胞骨动力学和神经元发射率.
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
- 分子生物学分子生物学
背景情况:
- 神经元发育涉及到动态的filopodia成熟成树突的棘.
- 树突性和棘对突触功能至关重要,并对细胞外线索做出反应.
- 众所周知,E3泛基因酶TRIM9 (三方基因含蛋白9) 能够调节神经元早期发育.
研究的目的:
- 为了研究TRIM9在树突型和脊柱中的作用,在synaptogenesis期间.
- 为了确定TRIM9对网-1.0的突触反应的要求.
- 阐明TRIM9在 postsynaptic密度 (PSD) 调节和细胞骨动态中的功能.
主要方法:
- 在小鼠皮层和海马神经元中对TRIM9的免疫定位.
- 神经元中的Trim9的遗传删除.
- 对PSD的蛋白质组分析.
- 评估动因细胞骨动力学 (Arp2/3复合积累).
- 测量突触受体变化和神经元发射速率.
主要成果:
- 在合成生成过程中,TRIM9局部化到树突型和棘.
- 失去Trim9会破坏对网-1的突触反应.
- 在Trim9中删除会改变PSD蛋白质组和actin细胞骨的格局.
- 在树突脊柱中,网氨酸诱导的氨酸积累在Trim9淘汰神经元中受损.
- 丧失Trim9会导致突触受体的改变,并降低了依赖网林的神经元发射速率的增加.
结论:
- TRIM9对于调节树突脊柱内细胞骨动力学至关重要.
- TRIM9在中介神经元对突触网-1信号传递的反应中发挥着至关重要的作用.
- 对于适当的突触功能和神经元刺激性,TRIM9是响应细胞外线索的必要条件.
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