TSC2 mediates hyperosmotic stress-induced inactivation of mTORC1

Scientific Reports
Monika PlescherConstantinos Demetriades

Abstract

mTOR complex 1 (mTORC1) regulates cell growth and metabolism. mTORC1 activity is regulated via integration of positive growth-promoting stimuli and negative stress stimuli. One stress cells confront in physiological and pathophysiological contexts is hyperosmotic stress. The mechanism by which hyperosmotic stress regulates mTORC1 activity is not well understood. We show here that mild hyperosmotic stress induces a rapid and reversible inactivation of mTORC1 via a mechanism involving multiple upstream signaling pathways. We find that hyperosmotic stress causes dynamic changes in TSC2 phosphorylation by upstream kinases, such as Akt, thereby recruiting TSC2 from the cytoplasm to lysosomes where it acts on Rheb, the direct activator of mTORC1. This work puts together a signaling pathway whereby hyperosmotic stress inactivates mTORC1.

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Citations

Feb 13, 2016·Nature Communications·Constantinos DemetriadesAurelio A Teleman
Mar 16, 2017·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Kuo-Hui Su, Chengkai Dai
Mar 18, 2017·Scientific Reports·Ahmad MerhiAnna Maria Marini
Jan 4, 2018·Cellular Logistics·Thu P NguyenJenna L Jewell
Jun 5, 2019·Molecular and Cellular Biology·Naoki TamuraSatoshi Waguri
Jan 18, 2017·The EMBO Journal·Asier González, Michael N Hall
Oct 28, 2019·Frontiers in Endocrinology·Zaixin Guo, Qi Yu
Aug 29, 2020·Genes·Chase H Melick, Jenna L Jewell
Feb 10, 2021·Biochemical and Biophysical Research Communications·Harleen Kaur, Régis Moreau

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Methods Mentioned

BETA
GTPase
dissect
GTPases
electrophoresis

Software Mentioned

ImageJ
Osmostress
ImageStudio

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