期刊
DEVELOPMENTAL CELL
卷 36, 期 2, 页码 139-151出版社
CELL PRESS
DOI: 10.1016/j.devcel.2015.12.019
关键词
-
资金
- Intellectual and Developmental Disabilities Research Center (NIH) [1U54 HD083092]
- Developmental Biology Program Training Grant NICHD [T32HD055200]
- NIH [R01-NS069880, 1RC4GM096355-01]
- Robert A. and Renee E. Belfer Family Foundation
- Huffington Foundation
- Target ALS
The ability to sense energy status is crucial in the regulation of metabolism via the mechanistic Target of Rapamycin Complex 1 (mTORC1). The assembly of the TTT-Pontin/Reptin complex is responsive to changes in energy status. Under energy-sufficient conditions, the TTT-Pontin/Reptin complex promotes mTORC1 dimerization and mTORC1-Rag interaction, which are critical for mTORC1 activation. We show that WAC is a regulator of energy-mediated mTORC1 activity. In a Drosophila screen designed to isolate mutations that cause neuronal dysfunction, we identified wacky, the homolog of WAC. Loss of Wacky leads to neurodegeneration, defective mTOR activity, and increased autophagy. Wacky and WAC have conserved physical interactions with mTOR and its regulators, including Pontin and Reptin, which bind to the TTT complex to regulate energy-dependent activation of mTORC1. WAC promotes the interaction between TTT and Pontin/Reptin in an energy-dependent manner, thereby promoting mTORC1 activity by facilitating mTORC1 dimerization and mTORC1-Rag interaction.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据