肌肉产生的局部释放的BDNF调节了神经肌肉突触中的突触后装置的初始形成
Jinkai Zhang1, Hiu-Lam Rachel Kwan2, Chi Bun Chan3
1Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong, China.
Cell death and differentiation
|November 7, 2024
概括
肌肉细胞产生来自大脑的神经营养因子 (BDNF),这对神经肌肉结 (NMJ) 发育至关重要. 这项研究揭示了类似于体的结构如何调节BDNF释放,影响乙胆受体聚类和NMJ形成.
科学领域:
- 肌肉生物学 肌肉生物学
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
背景情况:
- 脑衍生神经营养因子 (BDNF) 是一种参与肌肉新陈代谢的肌.
- 肌肉产生的BDNF在神经肌肉结 (NMJ) 发育中的作用基本上是未知的.
- 监管BDNF囊泡贩运,局部化,加工和释放在NMJs需要调查.
研究的目的:
- 研究肌肉产生的BDNF在NMJ发育中的作用.
- 阐明调节肌肉细胞中BDNF贩运,局部化和释放的机制.
- 确定BDNF在NMJ形成期间对乙胆受体 (AChR) 聚类的影响.
主要方法:
- 一个Xenopus肌肉细胞的初级细胞培养.
- 活细胞时间延迟成像.
- 降低BDNF并抑制氨酸活性.
- 骨肌特异性BDNF淘汰 (MBKO) 的小鼠模型.
- 对ACHR集群形成和定位的分析.
主要成果:
- 在肌肉细胞中,BDNF与肌肉细胞中的ACHR集群中的Podosome-like Structures (PLSs) 空间相关.
- 活动调节的,依赖的机制控制BDNF从PLS中的囊泡释放.
- 降低BDNF或抑制furin会损害神经动脉中AChR集群的形成和随后的突触集群.
- 在早期的NMJ发育过程中,MBKO小鼠显示出神经脉和突触AChR集群形成的缺陷.
结论:
- 类似Podosome的结构调节细胞内流通,空间定位和肌肉细胞中BDNF的活动依赖释放.
- 肌肉产生的BDNF及其蛋白质分解处理对于动脉神经和突触 AChR 集群的初始形成至关重要.
- 这项研究揭示了肌肉衍生的BDNF在脊椎动物NMJ发育中的新型调节作用.
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