Dynamics of mTORC1 activation in response to amino acids
What this study shows
Live imaging shows mTORC1 moves to lysosomes within 2 minutes of amino acid addition and peaks by 5 minutes, in step with leucine arriving in lysosomes; phosphorylation of classic mTORC1 targets lags behind, suggesting mTORC1 passes briefly through the lysosome before acting on substrates elsewhere.
Abstract
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Amino acids are essential activators of mTORC1 via a complex containing RAG GTPases, RAGULATOR and the vacuolar ATPase. Sensing of amino acids causes translocation of mTORC1 to lysosomes, an obligate step for activation. To examine the spatial and temporal dynamics of this translocation, we used live imaging of the mTORC1 component RAPTOR and a cell permeant fluorescent analogue of di-leucine methyl ester. Translocation to lysosomes is a transient event, occurring within 2 min of aa addition and peaking within 5 min.
Read the full abstract on PubMed →At a glance
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| Evidence type | M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: HEK293 cells; live imaging of RAPTOR and a fluorescent di-leucine analogue) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is. |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | HEK293 cells; live imaging of RAPTOR and a fluorescent di-leucine analogue |
| Journal | eLife |
| Year | 2016 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.7554/eLife.19960 · PMID 27725083 · Free full text (PMC5059141) |
Where this study fits
How this study connects to the pathway map, open questions, people and other studies in the Atlas.
People in the Atlas
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Cell biologist in Nicholas Ktistakis's group at the Babraham Institute whose live-cell imaging work spans more than two decades of research on lipid signalling, autophagosome formation and mTORC1
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Uses live imaging to follow the first minutes of autophagy and of mTORC1 activation
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Showed as a postdoc that mTORC1 senses amino acids from inside the lysosome, through the v-ATPase and Ragulator. His Berkeley lab has since mapped how the Rag GTPases and the folliculin complex switch mTORC1 on, and how lysosomal cholesterol feeds into the same system
More: 5 other authors
No profile yet: Smith M, Rotondo S, Walker S, Niewczas I, Clark J
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Topics
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | Amino acid add-back |
| Target | mTORC1 / RAPTOR lysosomal translocation |
| Model | Human cell line |
| Effect | mTORC1 lysosomal translocation is transient (2-5 min) and precedes target phosphorylation |
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