Amino acid signalling upstream of mTOR

Amino acids are one of the key environmental stimuli signalling to mTOR. Although exactly how they are sensed and how they activate mTOR has remained elusive, a model has emerged that implicates signalling by RAG GTPases, Ragulator and v-ATPase at the lysosome and leucyl t-RNA synthetase in the cytoplasm. Mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that is part of mTOR complex 1 (mTORC1), a master regulator that couples amino acid availability to cell growth and autophagy. Multiple cues modulate mTORC1 activity, such as growth factors, stress, energy status and amino acids. Although amino acids are key environmental stimuli, exactly how they are sensed and how they activate mTORC1 is not fully understood. Recently, a model has emerged whereby mTORC1 activation occurs at the lysosome and is mediated through an amino acid sensing cascade involving RAG GTPases, Ragulator and vacuolar H+-ATPase (v-ATPase).