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Rheb localized on the Golgi membrane activates lysosome-localized mTORC1 at the Golgi-lysosome contact site

Feike Hao1, Kazuhiko Kondo2, Takashi Itoh1

  • 1Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Osaka 565-0871, Japan.

Journal of Cell Science
|December 10, 2017
PubMed

Insights

The Golgi, not the lysosome, hosts Rheb which activates mTORC1 (mechanistic Target of Rapamycin Complex 1) at newly found Golgi-lysosome contact sites (GLCSs) crucial for cell growth regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • mTORC1 (mechanistic Target of Rapamycin Complex 1) regulates cell growth in response to nutrients.
  • mTORC1 activation is linked to its recruitment to the lysosome by Rheb.
  • The precise localization of Rheb for mTORC1 activation remains debated.

Purpose of the Study:

  • To investigate the intracellular localization of Rheb.
  • To determine the role of Golgi-Rheb interaction in mTORC1 activation.
  • To identify novel sites of inter-organelle communication regulating mTORC1.

Main Methods:

  • ব্যবহার of GFP-tagged Rheb to track its localization.
  • Forced mislocalization experiments of Rheb and mTORC1.
  • Microscopy to identify and quantify Golgi-lysosome contact sites (GLCSs).
  • Perturbation of GLCSs to assess mTORC1 activation.

Main Results:

  • Rheb predominantly localizes to the Golgi, not the lysosome.
  • Golgi-localized Rheb can activate mTORC1.
  • A novel organelle contact, the Golgi-lysosome contact site (GLCS), was discovered.
  • GLCS formation increases with amino acid supply, and its disruption inhibits mTORC1 activation.

Conclusions:

  • Rheb's role in mTORC1 activation occurs at the Golgi.
  • Golgi-lysosome contact sites (GLCSs) are critical regulators of mTORC1 signaling.
  • Inter-organelle communication between the Golgi and lysosome is essential for nutrient sensing and cell growth control.
Keywords:
GolgiLysosomeOrganelle contact siteRhebmTORC1

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