通过TMEM16F进行脂质杂乱,调解细胞外囊泡的形成和释放
Trieu Le1, Maria Eugenia Perez Collado2,3, Yu Meng Li1
1Program in Cell and Systems Biology or Peter Gilgan Centre for Research and Learning, SickKids Research Institute, 686 Bay St, Toronto, ON, Canada.
编程细胞死亡涉及囊泡释放. 仅仅是脂质杂乱,没有其他亡信号,可以通过改变膜曲率来触发这些小囊泡的形成.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 膜动力学 膜动力学
背景情况:
- 编程细胞死亡途径对于组织发育和平衡至关重要.
- 亡细胞释放膜片段,包括亡体和较小的囊泡.
- 亡体形成的机制已知,但囊泡生物发生的理解较少.
研究的目的:
- 为了研究脂质杂乱在编程细胞死亡期间囊泡中的作用.
- 为了确定单独的脂质混杂是否可以诱导囊泡释放,而不依赖于其他亡信号事件.
主要方法:
- 使用一种可诱导的,活性形式的TMEM16F来诱导等离子体lemmal脂质杂乱.
- 分析了囊泡释放,细胞质水平和子膜细胞骨架完整性.
- 检查了血膜中的脂质分布和膜曲率变化.
主要成果:
- 血体脂质杂乱诱导了类似apoptotic的囊泡的释放,而没有改变细胞质或细胞骨.
- 杂乱的膜显示了脂质分离和胆固醇再分配到内部的小册子.
- 甲基乙醇胺 (PE) 的积累和组件的聚合诱导了膜曲,促进了囊泡裂变.
结论:
- 脂质杂乱足以诱导类似于在亡细胞中观察到的囊泡.
- TMEM16F介导的脂质杂乱驱动了外向和内向膜曲率的形成.
- 这一过程促进了囊泡从血中脱离,从而导致细胞死亡形态.
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