Molecular mechanism to target the endosomal Mon1-Ccz1 GEF complex to the pre-autophagosomal structure
- University of Osnabrück, Germany
- University of Groningen, University Medical Center Groningen, Netherlands
Abstract
During autophagy, a newly formed double membrane surrounds its cargo to generate the so-called autophagosome, which then fuses with a lysosome after closure. Previous work implicated that endosomal Rab7/Ypt7 associates to autophagosomes prior to their fusion with lysosomes. Here, we unravel how the Mon1-Ccz1 guanosine exchange factor (GEF) acting upstream of Ypt7 is specifically recruited to the pre-autophagosomal structure under starvation conditions. We find that Mon1-Ccz1 directly binds to Atg8, the yeast homolog of the members of the mammalian LC3 protein family. This requires at least one LIR motif in the Ccz1 C-terminus, which is essential for autophagy but not for endosomal transport. In agreement, only wild-type, but not LIR-mutated Mon1-Ccz1 promotes Atg8-dependent activation of Ypt7. Our data reveal how GEF targeting can specify the fate of a newly formed organelle and provide new insights into the regulation of autophagosome-lysosome fusion.
Article and author information
Author details
Christian Ungermann
Funding
Deutsche Forschungsgemeinschaft (UN111/7-3)
- Christian Ungermann
Deutsche Forschungsgemeinschaft (SFB 944)
- Daniel Kuemmel
ZonMw (VICI 016.130.606)
- Fulvio Reggiori
European Commission (Marie Skłodowska-Curie ITN)
- Fulvio Reggiori
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF Sinergia (CRSII3_154421)
- Fulvio Reggiori
Deutsche Forschungsgemeinschaft (SFB 944)
- Christian Ungermann
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Noboru Mizushima, The University of Tokyo, Japan
Version history
- Received: August 9, 2017
- Accepted: February 12, 2018
- Accepted Manuscript published: February 15, 2018 (version 1)
- Version of Record published: March 7, 2018 (version 2)
Copyright
© 2018, Gao 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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Molecular mechanism to target the endosomal Mon1-Ccz1 GEF complex to the pre-autophagosomal structure
eLife 7:e31145.
https://doi.org/10.7554/eLife.31145
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