拉格GTPases通过调节Drosophila中的v-ATPase组合来控制 lysosomal 酸化
Ying Zhou1, Xiaodie Yang1, Wenyu Xu1
1College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, China.
GDP-bound RagA通过破坏CCT-v-ATPase相互作用来促进溶解体酸化,这对细胞代谢和Drosophila饥饿期间的生存至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 代谢过程中的代谢.
背景情况:
- 拉格GTPases是营养感应和mTORC1信号的关键调节者.
- 大虫中与GDP结合的Raga促进了溶酶体酸化和自,以维持饥饿的生存.
研究的目的:
- 阐明GDP-bound RagA刺激 lysosome 酸化的机制.
- 研究CCT和v-ATPase相互作用在这个过程中的作用.
主要方法:
- 研究了Raga,CCT和v-ATPase之间的相互作用,使用Drosophila的敲击和救援实验.
- 评估了溶酶体酸性化和自性降解.
- 通过Lamtor4 Knockdown检查了 lysosomal局部化的作用.
主要成果:
- 与GDP结合的Raga破坏了细胞系CCT和v-ATPase亚单元V1.1之间的物理相互作用.
- 这种干扰促进了活跃的v-ATPase组合,并增强了 lysosomal 酸化.
- 镇压CCT组件在RagaRNAi中拯救了自溶酶体缺陷.
- 拉格GTPases的溶解体局部化对于调节酸化至关重要,正如Lamtor4敲击所显示的那样.
结论:
- 与GDP结合的Raga通过一种涉及CCT-v-ATPase相互作用的新机制调节 lysosomal 酸化.
- 这条通路对于在饥饿条件下维持细胞平衡至关重要.
- 突出了CCT和v-ATPase在溶酶功能中的相互作用.
更多相关视频
08:44Quantitative Cell Biology of Neurodegeneration in Drosophila Through Unbiased Analysis of Fluorescently Tagged Proteins Using ImageJ
Published on: August 3, 2018
08:43Detergent-assisted Reconstitution of Recombinant Drosophila Atlastin into Liposomes for Lipid-mixing Assays
Published on: July 3, 2019
相关概念视频
Coat Assembly and GTPases
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Rab Proteins
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Small GTPases - Ras and Rho
Three regulatory proteins control their activity:
GTPases and their Regulation
Large G-proteins,...
Rab Cascades
ATP Driven Pumps III: V-type Pumps
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...
