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Published on: October 23, 2018
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.
Abstract:
Mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1) is a major signalling kinase in cells that regulates proliferation and metabolism and is controlled by extrinsic and intrinsic signals. The lysosome has received considerable attention as a major hub of mTORC1 activation. However, mTOR has also been located to a variety of other intracellular sites, indicating the possibility of spatial regulation of mTORC1 signalling within cells. In particular, there have been numerous recent reports of mTORC1 activation associated with the Golgi apparatus. Here, we review the evidence for the regulation of mTORC1 signalling at the Golgi in mammalian cells. mTORC1 signalling is closely linked to the morphology of the Golgi architecture; a number of Golgi membrane tethers/scaffolds that influence Golgi architecture in mammalian cells that directly or indirectly regulate mTORC1 activation have been identified. Perturbation of the Golgi mTORC1 pathway arising from fragmentation of the Golgi has been shown to promote oncogenesis. Here, we highlight the potential mechanisms for the activation mTORC1 at the Golgi, which is emerging as a major site for mTORC1 signalling.
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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