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Regulation of mTORC1 by amino acids

Liron Bar-Peled1, David M Sabatini2

  • 1Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Trends in Cell Biology
|April 5, 2014
PubMed

Insights

The mechanistic target of rapamycin complex I (mTORC1) pathway regulates cell growth and is vital for nutrient sensing. Discoveries reveal a lysosome-based system involving Rags, Ragulator, GATOR, and FLCN complexes that communicates amino acid levels to mTORC1.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The mechanistic target of rapamycin complex I (mTORC1) pathway is a key regulator of cellular and organismal growth.
  • Hyperactivation of the mTORC1 pathway is linked to human diseases like cancer and diabetes.
  • mTORC1 activity is modulated by nutrient availability, particularly amino acids, which signal for its activation at the lysosome.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which amino acid availability is communicated to mTORC1.
  • To detail the components of the newly discovered lysosome-based signaling system that regulates mTORC1 activation.

Main Methods:

  • The study focuses on the discovery and characterization of signaling complexes at the lysosome.
  • Key components investigated include Ras-related GTPases (Rags), Ragulator, v-ATPase, GATOR (GAP activity towards Rags), and folliculin (FLCN) complexes.

Main Results:

  • A lysosome-based signaling system involving Rags, Ragulator, GATOR, and FLCN complexes has been identified.
  • This system mediates the communication of amino acid levels to mTORC1, regulating its activation at the lysosome.

Conclusions:

  • Understanding this amino acid-sensing pathway provides critical insights into cellular growth control.
  • This knowledge is crucial for developing therapeutic strategies for diseases associated with mTORC1 deregulation, such as cancer and diabetes.
Keywords:
GATOR complexRag GTPasesRagulatoramino acid sensingfolliculin

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