生物活性 | |||
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描述 | The vacuolar H+-ATPase (v-ATPase) is a universal component of eukaryotic organisms, which is present in both intracellular compartments and the plasma membrane. Its proton-pumping action creates the low intravacuolar pH, benefiting many processes such as, membrane trafficking, protein degradation, renal acidification, bone resorption, and tumor metastasis [1]. EN6 is a small-molecule activator of autophagy that covalently targets cysteine 277 in the ATP6V1A subunit of the lysosomal v-ATPase, which activates mechanistic target of rapamycin complex 1 (mTORC1) via the Rag guanosine triphosphatases. EN6-mediated ATP6V1A modification decouples the v-ATPase from the Rags, leading to inhibition of mTORC1 signaling, increased lysosomal acidification and activation of autophagy. EN6 clears TDP-43 aggregates, a causative agent in frontotemporal dementia, in a lysosome-dependent manner [2]. | ||
作用机制 | EN6 covalently binds to cysteine 277 in the ATP6V1A subunit of v-ATPase . |
实验方案 | |||
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1mg | 5mg | 10mg | |
1 mM 5 mM 10 mM |
2.71mL 0.54mL 0.27mL |
13.57mL 2.71mL 1.36mL |
27.15mL 5.43mL 2.71mL |
参考文献 |
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