Acute mTORC1 amino acid sensing beyond leucine/arginine and roles of GCN2/ATF4

Determine how mechanistic target of rapamycin complex 1 (mTORC1) activation is affected by amino acids other than leucine and arginine and elucidate the roles of the general amino acid sensors GCN2 and ATF4 in acute mTORC1 signaling cascades.

Background

mTORC1 integrates nutrient cues to regulate translation, with well-characterized sensors for leucine (Sestrin2) and arginine (CASTOR1 and SLC38A9) that modulate Rag GTPase–dependent lysosomal recruitment and activation by Rheb.

The review highlights that, while prolonged amino acid deprivation engages the integrated stress response via GCN2 and ATF4, the acute (short-term) roles of these general amino acid sensors in directly influencing mTORC1 signaling remain unsettled, particularly for amino acids beyond leucine and arginine.