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Key mediators of intracellular amino acids signaling to mTORC1 activation

Yehui Duan1, Fengna Li, Kunrong Tan

  • 1Chinese Academy of Science, Institute of Subtropical Agriculture, Research Center for Healthy Breeding Livestock and Poultry, Hunan Engineering and Research Center for Animal and Poultry Science, Key Laboratory of Agroecology in Subtropical Region, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central China, Ministry of Agriculture, Changsha, Hunan, 410125, People's Republic of China.

Amino Acids
|February 22, 2015
PubMed

Insights

Amino acids activate the mTORC1 pathway, controlling cell growth. This review details how mediators like Rag GTPases and Rheb regulate this complex signaling network.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Metabolism

Background:

  • Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell growth and protein synthesis.
  • Amino acid availability is a primary signal for mTORC1 activation, influencing cellular processes.
  • The precise molecular mechanisms linking amino acids to mTORC1 activation are intricate and involve multiple mediators.

Purpose of the Study:

  • To review the function of key mediators in the amino acid-activated mTORC1 pathway.
  • To elucidate the regulatory roles of these mediators in response to amino acid availability.
  • To discuss the complex signaling network controlling cellular growth, proliferation, and metabolism via mTORC1.

Main Methods:

  • Literature review of signaling pathways.
  • Analysis of molecular interactions between amino acids and mTORC1 mediators.
  • Discussion of regulatory mechanisms involving Rag GTPases, Rheb, hVps34, and MAP4K3.

Main Results:

  • Amino acids activate Rag GTPases, which translocate mTORC1 to late endosomes/lysosomes.
  • Rheb, located on endosomes/lysosomes, directly activates mTORC1.
  • hVps34 and MAP4K3 are additional mediators in amino acid signaling to mTORC1.

Conclusions:

  • The mTORC1 pathway integrates amino acid signals through a complex network of mediators.
  • Lysosomes and endosomes serve as critical platforms for amino acid sensing and mTORC1 activation.
  • Understanding this pathway is crucial for comprehending cellular growth, proliferation, and metabolic control.

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