The ULK1-FBXW5-SEC23B nexus controls autophagy
- New York University School of Medicine, United States
- Howard Hughes Medical Institute, University of California, Berkeley, United States
- Instituto de Investigación en Biomedicina de Buenos Aires, CONICET-Partner Institute of the Max Planck Society, Argentina
- The Stowers Institute for Medical Research, United States
- Albert Einstein College of Medicine, United States
Abstract
In response to nutrient deprivation, the cell mobilizes an extensive amount of membrane to form and grow the autophagosome, allowing the progression of autophagy. By providing membranes and stimulating LC3 lipidation, COPII (Coat Protein Complex II) promotes autophagosome biogenesis. Here, we show that the F-box protein FBXW5 targets SEC23B, a component of COPII, for proteasomal degradation and that this event limits the autophagic flux in the presence of nutrients. In response to starvation, ULK1 phosphorylates SEC23B on Serine 186, preventing the interaction of SEC23B with FBXW5 and, therefore, inhibiting SEC23B degradation. Phosphorylated and stabilized SEC23B associates with SEC24A and SEC24B, but not SEC24C and SEC24D, and they re-localize to the ER-Golgi intermediate compartment, promoting autophagic flux. We propose that, in the presence of nutrients, FBXW5 limits COPII-mediated autophagosome biogenesis. Inhibition of this event by ULK1 ensures efficient execution of the autophagic cascade in response to nutrient starvation.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Mass spectrometry data is available at http://www.stowers.org/research/publications/libpb‐1118 (ftp://odr.stowers.org/LIBPB-1118) and has also been deposited to the MassIVE repository. Source data files have been provided for Figures 1, 3, 4, 5, 6, 7, Figure 2-figure supplement 1, and Figure 4-figure supplement 1.
Article and author information
Author details
Michael P Washburn
Claudio N Cavasotto
Funding
National Institutes of Health (R01‐CA076584)
- Michele Pagano
National Institutes of Health (R01‐GM057587)
- Michele Pagano
Agencia Nacional de Promoción Científica y Tecnológica (PICT‐2014‐0458)
- Mario Rossi
Agencia Nacional de Promoción Científica y Tecnológica (PICT2016‐2620)
- Mario Rossi
Agencia Nacional de Promoción Científica y Tecnológica (PICT‐ 2014‐3599)
- Claudio N Cavasotto
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Jeong et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The ULK1-FBXW5-SEC23B nexus controls autophagy
eLife 7:e42253.
https://doi.org/10.7554/eLife.42253
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