Cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1)

Cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1) is a cytosolic protein that functions as a direct sensor of intracellular arginine concentrations. It plays a pivotal role in regulating the mechanistic target of rapamycin complex 1 (mTORC1) pathway, which controls cell growth, metabolism, and autophagy in response to nutrient availability. CASTOR1 exists as a homodimer, each monomer containing four tandem ACT domains that structurally resemble the regulatory domains of prokaryotic aspartate kinases. In the absence of arginine, CASTOR1 binds the GATOR2 complex, thereby inhibiting mTORC1 activation. When arginine is present, it binds to a specialized pocket at the interface of ACT2 and ACT4 domains on CASTOR1, causing a conformational change that leads to dissociation from GATOR2 and activation of mTORC1 signaling. This arginine-dependent regulatory mechanism is critical for the fine-tuning of mTORC1’s control over anabolic processes and has implications in diseases such as cancer and metabolic disorders due to deregulation of nutrient sensing and mTORC1 activity

Other names

Cellular arginine sensor for mTORC1 protein 1GATS-like protein 3GATSL3GATSL3 proteinGATS protein like 3

Allosteric modulation (arginine binding disrupts CASTOR1–GATOR2 interaction to activate mTORC1)