Regulation of mTORC1 activity by the Golgi apparatus

Christian Makhoul1, Paul A Gleeson1

  • 1The Department of Biochemistry and Pharmacology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.

Faculty Reviews
|July 1, 2021
PubMed

Insights

The mechanistic target of rapamycin complex 1 (mTORC1) pathway is regulated at the Golgi apparatus, a distinct cellular site from the lysosome. This Golgi-centric mTORC1 signaling is linked to cell proliferation and oncogenesis.

Area of Science:

  • Cell Biology
  • Molecular Signaling
  • Cancer Research

Background:

  • Mechanistic target of rapamycin complex 1 (mTORC1) is a key regulator of cell proliferation and metabolism.
  • While lysosomes are known mTORC1 hubs, mTORC1 signaling is also spatially regulated at other intracellular sites.
  • Recent evidence suggests the Golgi apparatus is a significant site for mTORC1 activation.

Purpose of the Study:

  • To review the evidence for mTORC1 signaling regulation at the Golgi apparatus in mammalian cells.
  • To highlight the mechanisms of mTORC1 activation at the Golgi.
  • To discuss the link between Golgi-associated mTORC1 signaling and oncogenesis.

Main Methods:

  • Literature review of studies investigating mTORC1 signaling at the Golgi.
  • Analysis of the relationship between Golgi architecture and mTORC1 activation.
  • Discussion of potential molecular mechanisms for Golgi-based mTORC1 regulation.

Main Results:

  • mTORC1 signaling is demonstrably regulated at the Golgi apparatus.
  • Specific Golgi membrane tethers and scaffolds directly or indirectly influence mTORC1 activation.
  • Perturbation of Golgi mTORC1 signaling, through Golgi fragmentation, is linked to oncogenesis.

Conclusions:

  • The Golgi apparatus is an emerging major site for mTORC1 signaling.
  • Spatial regulation of mTORC1 at the Golgi plays a role in cellular processes and disease.
  • Understanding Golgi-mTORC1 interactions is crucial for cancer research.

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