The ULK1-FBXW5-SEC23B nexus controls autophagy

Yeon Tae Jeong, Daniele Simoneschi, Sarah Keegan, David Melville, Natalia S. Adler, Anita Saraf, Laurence Florens, Michael P. Washburn, Claudio N. Cavasotto, David Fenyö, Ana Maria Cuervo, Mario Rossi, Michele Pagano

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Article numbere42253
JournaleLife
Volume7
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Jeong, Y. T., Simoneschi, D., Keegan, S., Melville, D., Adler, N. S., Saraf, A., Florens, L., Washburn, M. P., Cavasotto, C. N., Fenyö, D., Cuervo, A. M., Rossi, M., & Pagano, M. (2018). The ULK1-FBXW5-SEC23B nexus controls autophagy. eLife, 7, [e42253]. https://doi.org/10.7554/eLife.42253