Regulation of mTORC1 by amino acids

Trends Cell Biol. 2014 Jul;24(7):400-6. doi: 10.1016/j.tcb.2014.03.003. Epub 2014 Mar 31.

Abstract

The mechanistic target of rapamycin complex I (mTORC1) is a central regulator of cellular and organismal growth, and hyperactivation of this pathway is implicated in the pathogenesis of many human diseases including cancer and diabetes. mTORC1 promotes growth in response to the availability of nutrients, such as amino acids, which drive mTORC1 to the lysosomal surface, its site of activation. How amino acid levels are communicated to mTORC1 is only recently coming to light by the discovery of a lysosome-based signaling system composed of Rags (Ras-related GTPases) and Ragulator v-ATPase, GATOR (GAP activity towards Rags), and folliculin (FLCN) complexes. Increased understanding of this pathway will not only provide insight into growth control but also into the human pathologies triggered by its deregulation.

Keywords: GATOR complex; Rag GTPases; Ragulator; amino acid sensing; folliculin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Humans
  • Lysosomes / metabolism
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / metabolism*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Amino Acids
  • Multiprotein Complexes
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1