Amino acid and small GTPase regulation of mTORC1

Thu P Nguyen1,2, Anderson R Frank1,2, Jenna L Jewell1,2

  • 1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX USA.

Cellular Logistics
|January 4, 2018
PubMed

Insights

Amino acids regulate cell growth via the mammalian target of rapamycin (mTOR) kinase. This review details how specific amino acids activate mTOR complex 1 (mTORC1) through distinct nutrient-sensing pathways.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • The mammalian target of rapamycin (mTOR) is a key regulator of cell growth and metabolism.
  • mTOR functions as the catalytic subunit of mTOR complex 1 (mTORC1).
  • Amino acids are potent stimuli for mTORC1 activation, integrating environmental signals.

Purpose of the Study:

  • To review the mechanisms by which amino acids modulate mTORC1 activity.
  • To highlight the differential regulation of mTORC1 by specific amino acids.
  • To discuss the role of small GTPases in mTORC1 regulation.

Main Methods:

  • Literature review of studies on mTORC1 signaling.
  • Analysis of nutrient-sensing pathways.
  • Focus on Rag GTPase-dependent and -independent mechanisms.

Main Results:

  • Leucine and arginine activate mTORC1 via Rag GTPases.
  • A distinct, Rag GTPase-independent glutamine pathway to mTORC1 has been identified.
  • mTORC1 is differentially regulated by specific amino acids through distinct signaling routes.

Conclusions:

  • Amino acid availability is a critical determinant of mTORC1 activity.
  • Multiple nutrient-sensing pathways converge on mTORC1.
  • Understanding these pathways is crucial for comprehending cell growth and metabolism control.

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