Models of amino acid-dependent mTORC1 regulation Models of amino acid-dependent mTORC1 regulation The presence of free amino acids is essential for the activation of mTORC1. Leucine, glutamine and arginine signal to mTORC1 by different mechanisms. These include cytoplasmic sensors, amino acid transporters and v-ATPase on the lysosomal membrane. The amino acid transporters sense specific amino acids in different subcellular compartments and act in cooperation with cytosolic amino acid sensors to control the activity of mTORC1. Other transporters act as conduits bringing amino acids inside the cell. All these mechanisms work to control the nucleotide-loading status of either Rag GTPases or Rheb, the most proximal regulators of mTORC1. mTORC1 hubs controlled by Arf1 and Rab1A/PAT4 appear to be Rag independent and are therefore not under the control of the cytosolic sensors. Arf1 is typically found on Golgi membranes but is reported to control a lysosomal sensing complex. Yoana Rabanal-Ruiz et al. Essays Biochem. 2017;61:565-584 ©2017 by Portland Press Ltd