Leucine
Branched-chain essential amino acid and the best-characterised nutrient input to mTORC1. Free leucine binds Sestrin2, releasing the GATOR2 brake; a competing model has leucyl-tRNA synthetase as the sensor instead.
The amino acid the cell watches most closely.
Binds Sestrin2 with ~20 µM Kd – within the range over which intracellular leucine actually fluctuates, which is the main argument that Sestrin2 is a physiological sensor rather than a binder.
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| M | Molecular — cells, biochemistry, structure | 5 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2017 | M | mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient WYA2017 SLC38A9 effluxes essential amino acids (e.g. leucine) from lysosomes to activate mTORC1. |
| 2015 | M | Sestrin2 is a leucine sensor for the mTORC1 pathway WOL2015 Sestrin2 is a direct leucine sensor whose leucine binding releases GATOR2 to activate mTORC1. |
| 2015 | M | Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway SAX2015 Solves the crystal structure of Sestrin2 bound to leucine, revealing the molecular pocket that lets it act as mTORC1's dedicated leucine sensor. |
| 2015 | M | Metabolism. Differential regulation of mTORC1 by leucine and glutamine JEW2015 Glutamine activates mTORC1 via a Rag-independent, Arf1-dependent route distinct from leucine. |
| 2012 | M | Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway HAN2012 Leucyl-tRNA synthetase acts as an intracellular leucine sensor activating mTORC1 via the Rag pathway. |