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TSC2 mediates hyperosmotic stress-induced inactivation of mTORC1

Monika Plescher1, Aurelio A Teleman1, Constantinos Demetriades1

  • 1Division of Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Scientific Reports
|September 9, 2015
PubMed

Insights

Mild hyperosmotic stress rapidly inactivates the cell growth regulator mTOR complex 1 (mTORC1). This occurs through dynamic changes in TSC2 phosphorylation, affecting its lysosomal recruitment and Rheb activity.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Metabolism Regulation

Background:

  • mTOR complex 1 (mTORC1) is a key regulator of cell growth and metabolism.
  • mTORC1 activity integrates growth signals and stress responses.
  • Hyperosmotic stress is a cellular stressor whose effect on mTORC1 is not fully understood.

Purpose of the Study:

  • To elucidate the mechanism by which hyperosmotic stress regulates mTORC1 activity.
  • To identify the signaling pathways involved in hyperosmotic stress-induced mTORC1 inactivation.

Main Methods:

  • Investigated the effects of mild hyperosmotic stress on mTORC1 signaling.
  • Analyzed dynamic changes in TSC2 phosphorylation and localization.
  • Examined the interaction between TSC2, Akt, and Rheb.

Main Results:

  • Mild hyperosmotic stress rapidly and reversibly inactivates mTORC1.
  • Hyperosmotic stress induces dynamic TSC2 phosphorylation by kinases like Akt.
  • TSC2 is recruited from the cytoplasm to lysosomes, impacting Rheb, the direct mTORC1 activator.

Conclusions:

  • A signaling pathway for hyperosmotic stress-induced mTORC1 inactivation has been identified.
  • This pathway involves dynamic TSC2 phosphorylation and lysosomal recruitment.
  • Understanding this mechanism is crucial for comprehending cellular responses to osmotic stress.

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