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The Golgi ribbon in mammalian cells negatively regulates autophagy by modulating mTOR activity.

Authors
  • Gosavi, Prajakta1
  • Houghton, Fiona J1
  • McMillan, Paul J1, 2
  • Hanssen, Eric1, 3
  • Gleeson, Paul A4
  • 1 The Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria 3010, Australia. , (Australia)
  • 2 Biological Optical Microscopy Platform, The University of Melbourne, Melbourne, Victoria 3010, Australia. , (Australia)
  • 3 Advanced Microscopy Facility, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria 3010, Australia. , (Australia)
  • 4 The Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria 3010, Australia [email protected] , (Australia)
Type
Published Article
Journal
Journal of Cell Science
Publisher
The Company of Biologists
Publication Date
Feb 08, 2018
Volume
131
Issue
3
Identifiers
DOI: 10.1242/jcs.211987
PMID: 29361552
Source
Medline
Keywords
License
Unknown

Abstract

In vertebrates, individual Golgi stacks are joined into a compact ribbon structure; however, the relevance of a ribbon structure has been elusive. Here, we exploit the finding that the membrane tether of the trans-Golgi network, GCC88 (encoded by GCC1), regulates the balance between Golgi mini-stacks and the Golgi ribbon. Loss of Golgi ribbons in stable cells overexpressing GCC88 resulted in compromised mechanistic target of rapamycin (mTOR) signaling and a dramatic increase in LC3-II-positive autophagosomes, whereas RNAi-mediated depletion of GCC88 restored the Golgi ribbon and reduced autophagy. mTOR was absent from dispersed Golgi mini-stacks whereas recruitment of mTOR to lysosomes was unaffected. We show that the Golgi ribbon is a site for localization and activation of mTOR, a process dependent on the ribbon structure. We demonstrate a strict temporal sequence of fragmentation of Golgi ribbon, loss of Golgi mTOR and subsequent increased autophagy. Golgi ribbon fragmentation has been reported in various neurodegenerative diseases and we demonstrate the potential relevance of our findings in neuronal cells using a model of neurodegeneration. Overall, this study highlights a role for the Golgi ribbon in pathways central to cellular homeostasis.This article has an associated First Person interview with the first author of the paper.

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