A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress
- Gregor Mendel Institute, Vienna Biocenter, Austria
- Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Austria
- The Chinese University of Hong Kong, Hong Kong
- Leibniz Institute of Plant Biochemistry, Germany
- University of Vienna, Austria
- Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC), Austria
- IPK Gatersleben, Germany
- University of Natural Resources and Life Sciences, Austria
- the Chinese University of Hong Kong, Hong Kong
- Research Institute of Molecular Pathology, Austria
- Medical Institute of Bioregulation (MIB), Kyushu University, Japan
Abstract
Eukaryotes have evolved various quality control mechanisms to promote proteostasis in the ER. Selective removal of certain ER domains via autophagy (termed as ER-phagy) has emerged as a major quality control mechanism. However, the degree to which ER-phagy is employed by other branches of ER-quality control remains largely elusive. Here, we identify a cytosolic protein, C53, that is specifically recruited to autophagosomes during ER-stress, in both plant and mammalian cells. C53 interacts with ATG8 via a distinct binding epitope, featuring a shuffled ATG8 interacting motif (sAIM). C53 senses proteotoxic stress in the ER lumen by forming a tripartite receptor complex with the ER-associated ufmylation ligase UFL1 and its membrane adaptor DDRGK1. The C53/UFL1/DDRGK1 receptor complex is activated by stalled ribosomes and induces the degradation of internal or passenger proteins in the ER. Consistently, the C53 receptor complex and ufmylation mutants are highly susceptible to ER stress. Thus, C53 forms an ancient quality control pathway that bridges selective autophagy with ribosome-associated quality control in the ER.
Data availability
All the raw data associated with the figures are uploaded to Dryad and accessible here doi:10.5061/dryad.wm37pvmkb. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD019988.
Article and author information
Author details
Funding
Vienna Science and Technology Fund (LS17-047)
- Madlen Stephani
- Lorenzo Picchianti
- Tim Clausen
- Yasin Dagdas
Austrian Science Fund (P32355)
- Yasin Dagdas
Austrian Science Fund (P30401-B21)
- Sascha Martens
Austrian Science Fund (I3033-B22)
- Armin Djamei
Austrian Science Fund (Unidocs fellowship)
- Adriana Savova
Austrian Academy of Sciences
- Alexander Gajic
- Emilio Skarwan
- Victor Sanchez de Medina Hernandez
- Azadeh Mohseni
- Marion Clavel
- Christian Loefke
- Alibek Abdrakhmanov
- Yasin Dagdas
Horizon 2020 Framework Programme (No.646653)
- Sascha Martens
The Financial Supports for Young Scientists International Research Scholarship Fund (BWM 315/2018)
- Mateusz Matuszkiewicz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Stephani 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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