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2+传感器ALG-2使用ESCRT来增强 lysosomal膜对透应激的弹性
Wei Chen1, Madeline M Motsinger1, Jiaqian Li1,2
1Department of Biological Chemistry, University of Michigan School of Medicine, Ann Arbor, MI 48109.
概括
细胞使用离子 (Ca2+) 来保护溶解体免受透应激. ,通过ALG-2,招募ESCRT蛋白来增强 lysosomal 膜的弹性并保持器官完整性.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 机体生物学 机体生物学
背景情况:
- 溶解体对于细胞代谢和信号传递至关重要.
- 溶酶体膜损伤会导致有毒物质的释放,损害细胞功能.
- 细胞必须有机制在压力下保持 lysosomal 完整性.
研究的目的:
- 为了研究细胞对溶解体中透应激的反应.
- 阐明 (Ca2+) 在 lysosomal 膜弹性中的作用.
- 为了识别参与在透应激过程中维护 lysosomal 完整性的蛋白质.
主要方法:
- 使用敏感测试来测量由甘氨酸-L-氨酸2-纳胺 (GPN) 诱导的溶酶体泄漏和破裂.
- 操纵了细胞质和近溶酶体Ca2+水平.
- 评估了亡相关基因-2 (ALG-2) 和需要用于运输 (ESCRT) 蛋白质的内体排序复合体的招募和功能.
主要成果:
- 低GPN度诱导了大多数溶解体的Ca2+释放和小部分的破裂.
- 化细胞质Ca2+增加了对GPN诱导破裂的溶解体敏感性.
- 由GPN诱导的Ca2+释放触发了ALG-2和ESCRT蛋白质在溶解体中的招募.
- ALG-2,但不是它的ESCRT结合-disabled变体,增强了对透应激的溶酶体弹性.
- 激活TRPML1以提升Ca2+而不会损伤膜也招募了ALG-2和ESCRT,赋予了保护.
结论:
- Ca2+在维持 lysosomal 膜抵抗透应激的弹性方面发挥着至关重要的作用.
- Ca2+传感器ALG-2与ESCRT蛋白结合,调解这种保护机制.
- 这一途径增强了 lysosomal 完整性,防止有机体破裂和压力下内容泄漏.
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