Cellular arginine sensor for mTORC1 (CASTOR) (CASTOR)

The Cellular arginine sensor for mTORC1 (CASTOR) family, primarily consisting of CASTOR1 and CASTOR2, serves as a critical nutrient-sensing mechanism that regulates the mechanistic target of rapamycin complex 1 (mTORC1) pathway in response to arginine availability (Chantranupong et al., 2016, Cell). CASTOR1 functions as a homodimer or a heterodimer with CASTOR2 and directly binds L-arginine through its ACT domains (Saxton et al., 2016, Science). In the absence of arginine, CASTOR1 binds to and inhibits GATOR2, a positive regulator of mTORC1, thereby keeping the pathway inactive (Gai et al., 2016, Nature). When arginine levels are sufficient, the amino acid binds to CASTOR1, inducing a conformational change that triggers its dissociation from GATOR2, which then allows for mTORC1 activation at the lysosomal surface (UniProt Q8WUX7). Because the mTORC1 pathway is frequently dysregulated in various pathologies, the CASTOR family represents a potential therapeutic target for treating cancer and metabolic disorders (Wolfson & Sabatini, 2017, Science). Modulating CASTOR activity could provide a more specific way to control mTORC1 signaling compared to broad-spectrum inhibitors like rapamycin.

Other names

CASTOR1CASTOR2GATOR2-interacting proteinGATOR2-IPCellular arginine sensor for mTORC1 protein 1Cellular arginine sensor for mTORC1 protein 2

CASTOR1 acts as a negative regulator of mTORC1 by sequestering GATOR2 in arginine-depleted conditions; arginine binding triggers CASTOR1 dissociation from GATOR2, enabling mTORC1 activation (Chantranupong et al., 2016, Cell; Saxton et al., 2016, Science).