CASTOR1
Direct cytosolic arginine sensor for the mTORC1 pathway; arginine binding releases its inhibition of GATOR2.
An arginine detector that works as a brake. A sensor inside the cell that directly detects the amino acid arginine. When arginine binds it, it releases its grip on GATOR2, allowing mTORC1 signaling to proceed.
Homodimer (or heterodimer with CASTOR2); arginine binding dissociates it from GATOR2. Same double-negative logic as Sestrin2.
TL;DR. CASTOR1 appears in 4 curated studies in Oliver's mTOR Atlas: 3 at the molecular level (cells, biochemistry, structure); 1 review. No study in people is recorded for it in the Atlas yet. It has 2 interactions in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| CASTOR1 inhibits GATOR2 mechanism: binding · this link in full · on the map table | Without arginine, CASTOR1 holds onto GATOR2 and keeps the pathway switched off. Arginine-free CASTOR1 binds GATOR2 and inhibits it, so the pathway stays off until arginine is available. Arginine-free CASTOR1 binds GATOR2 and inhibits it, so the pathway stays off until arginine is available. Holds under: Human cell biochemistry and structure (CHA2016, SAX2016). The binding is shown in cells; there is no whole-animal or human test in the cited studies. plausible in people, not shown directly · settled in the literature | M | CHA2016, SAX2016 |
| Arginine inhibits CASTOR1 mechanism: binding · this link in full · on the map table | Arginine sticks to CASTOR1 the same way leucine sticks to Sestrin2 – the same trick, for a different amino acid. Cytosolic arginine binds CASTOR1 and breaks its grip on GATOR2 - the same trick as leucine/Sestrin2, but for a different amino acid. Cytosolic arginine binds CASTOR1 and breaks its grip on GATOR2 - the same trick as leucine/Sestrin2, but for a different amino acid. Holds under: Human cells and structural work (CHA2016, SAX2016). Shows how arginine is sensed in cells. Whether this sensor matters for arginine supply in a whole animal or a person is not tested here. plausible in people, not shown directly · settled in the literature | M | CHA2016, SAX2016 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| M | Molecular — cells, biochemistry, structure | 3 |
| R | Review — secondary literature, not a new result | 1 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2026 | M | CASTOR1 regulates humoral immune responses and contributes to the pathogenesis of systemic lupus erythematosus KUS2026 Gives the arginine sensor CASTOR1 a defined physiological job upstream of mTORC1: losing it de-represses mTORC1 in B cells and drives plasma-cell expansion, IgG and anti-dsDNA autoantibodies, and lupus-like glomerulonephritis. In human SLE, CASTOR1 expression in plasmablasts was inversely correlated with disease activity (r = -0.32, p = 0.00031). One of the few studies to tie a specific upstream amino-acid sensor to a human autoimmune phenotype rather than to cancer or growth. |
| 2022 | M | Structure of the nutrient-sensing hub GATOR2 VAL2022 Cryo-EM structure of human GATOR2: a 1.1 MDa, two-fold symmetric cage built on an octagonal scaffold decorated with eight pairs of WD40 beta-propellers, and a map of where Sestrin2 and CASTOR1 dock. It substantially advances the GATOR2 side of the sensor module, though how GATOR2 inhibits GATOR1 is still not fully settled. |
| 2017 | R | The Dawn of the Age of Amino Acid Sensors for the mTORC1 Pathway WOLF2017 Review of the newly discovered amino-acid sensors feeding into mTORC1. |
| 2016 | M | The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway CHA2016 Identified CASTOR1 as the direct arginine sensor: when arginine binds CASTOR1, it lets go of GATOR2, switching mTORC1 on. Together with Sestrin2 (leucine) this built the picture of mTORC1 as a cell that literally tastes individual amino acids. |
Related entities
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