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Functional interaction of mammalian target of rapamycin complexes in regulating mammalian cell size and cell cycle

Margit Rosner1, Christiane Fuchs, Nicol Siegel

  • 1Medical Genetics, Medical University of Vienna, 1090 Vienna, Austria.

Human Molecular Genetics
|June 10, 2009
PubMed

Insights

The mammalian target of rapamycin (mTOR) pathway regulates cell growth. This study reveals that mTORC2, not just mTORC1, controls cell size and cell cycle via the Akt/TSC2/Rheb pathway, impacting human diseases.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Dysregulation of the mammalian target of rapamycin (mTOR) kinase pathway is implicated in numerous cancers and genetic disorders.
  • mTOR exists in two complexes: mTORC1 and mTORC2, with mTORC1 known to regulate cell size and cycle.
  • The role of mTORC2 in cell size and cell cycle control remained largely undetermined.

Purpose of the Study:

  • To investigate the specific roles of mTORC1 and mTORC2 in regulating mammalian cell size and cell cycle.
  • To elucidate the mechanism by which mTORC2 influences cell size and cell cycle progression.

Main Methods:

  • Investigated the functional separation of mTORC1-mediated effects on cell cycle and cell size.
  • Assessed the impact of mTORC1 on mTORC2 activity.
  • Examined the role of mTORC2 in regulating cell size and cell cycle through the Akt/TSC2/Rheb signaling cascade.

Main Results:

  • mTORC1-mediated effects on cell cycle and cell size are distinct and do not affect mTORC2 activity.
  • mTORC2 was identified as a significant regulator of mammalian cell size.
  • mTORC2 controls cell cycle progression through the Akt/TSC2/Rheb pathway.

Conclusions:

  • The findings delineate separable roles for mTORC1 and mTORC2 in cellular regulation.
  • mTORC2 plays a critical role in controlling mammalian cell size and cell cycle.
  • Understanding mTORC2's function provides insights into human diseases linked to mTOR pathway deregulation.

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