mTORC1 Senses Lysosomal Amino Acids Through an Inside-Out Mechanism That Requires the Vacuolar H + -ATPase
Broad Institute · Allen Institute · +4 more institutions
Abstract
The mTOR complex 1 (mTORC1) protein kinase is a master growth regulator that is stimulated by amino acids. Amino acids activate the Rag guanosine triphosphatases (GTPases), which promote the translocation of mTORC1 to the lysosomal surface, the site of mTORC1 activation. We found that the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1. The v-ATPase engages in extensive amino acid-sensitive interactions with the Ragulator, a scaffolding complex that anchors the Rag GTPases to the lysosome. In a cell-free system, ATP hydrolysis by the v-ATPase was necessary for amino acids to regulate the v-ATPase-Ragulator interaction and promote mTORC1 translocation.…
Citation impact
- FWCI
- 40.30
- Percentile
- 100%
- References
- 26
Authors
6- RZRoberto Zoncu
Broad Institute, Allen Institute, Whitehead Institute for Biomedical Research, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology
- LBLiron Bar‐Peled
Allen Institute, Whitehead Institute for Biomedical Research, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology
- AEAlejo Efeyan
Allen Institute, Whitehead Institute for Biomedical Research, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology
- SWShuyu Wang
Allen Institute, Whitehead Institute for Biomedical Research, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology
- YSYasemin Sancak
Allen Institute, Whitehead Institute for Biomedical Research, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology
Topics & keywords
- Vacuole
- Mechanism (biology)
- ATPase
- Chemistry
- mTORC1
- V-ATPase
- Amino acid
- Lysosome