Mechanism of cargo-directed Atg8 conjugation during selective autophagy
- University of Vienna, Austria
Abstract
Selective autophagy is mediated by cargo receptors that link the cargo to the isolation membrane via interactions with Atg8 proteins. Atg8 proteins are localized to the membrane in an ubiquitin-like conjugation reaction, but how this conjugation is coupled to the presence of the cargo is unclear. Here we show that the S. cerevisiae Atg19, Atg34 and the human p62, Optineurin and NDP52 cargo receptors interact with the E3-like enzyme Atg12∼Atg5-Atg16, which stimulates Atg8 conjugation. The interaction of Atg19 with the Atg12∼Atg5-Atg16 complex is mediated by its Atg8-interacting motifs (AIMs). We identify the AIM-binding sites in the Atg5 subunit and mutation of these sites impairs selective autophagy. In a reconstituted system the recruitment of the E3 to the prApe1 cargo is sufficient to drive accumulation of conjugated Atg8 at the cargo. The interaction of the Atg12∼Atg5-Atg16 complex and Atg8 with Atg19 is mutually exclusive, which may confer directionality to the system.
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Author details
Funding
European Research Council (260304)
- Sascha Martens
European Research Council (646653)
- Sascha Martens
European Research Council (279408)
- Bojan Zagrovic
Austrian Science Fund (P25546-B20)
- Sascha Martens
Austrian Science Fund (P25522-B20)
- Claudine Kraft
Austrian Science Fund (P28113-B28)
- Claudine Kraft
Austrian Science Fund (T724-B20)
- Justyna Sawa-Makarska
Vienna Science and Technology Fund (VRG10-791 001)
- Claudine Kraft
European Molecular Biology Organization (YIP)
- Claudine Kraft
- Sascha Martens
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2016, Fracchiolla 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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Mechanism of cargo-directed Atg8 conjugation during selective autophagy
eLife 5:e18544.
https://doi.org/10.7554/eLife.18544
