Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy
- Goethe University School of Medicine, Germany
- University of Groningen, University Medical Center Groningen, Netherlands
- Goethe University Frankfurt, Germany
- Lerner Research Institute, United States
Abstract
The turnover of endoplasmic reticulum (ER) ensures the correct biological activity of its distinct domains. In mammalian cells the ER is degraded via a selective autophagy pathway (ER-phagy), mediated by two specific receptors: FAM134B, responsible for the turnover of ER sheets and SEC62 that regulates ER recovery following stress. Here we identified reticulon 3 (RTN3) as a specific receptor for the degradation of ER tubules. Oligomerization of the long isoform of RTN3 is sufficient to trigger fragmentation of ER tubules. The long N-terminal region of RTN3 contains several newly identified LC3-interacting regions (LIR). Binding to LC3s/GABARAPs is essential for the fragmentation of ER tubules and their delivery to lysosomes. RTN3-mediated ER-phagy requires conventional autophagy components, but is independent of FAM134B. None of the other reticulon family members have the ability to induce fragmentation of ER tubules during starvation. Therefore, we assign a unique function to RTN3 during autophagy.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (Collaborative Research Centre on Selective Autophagy SFB 1177)
- Mike Heilemann
- Ivan Dikic
Cluster of Excellence Goethe University Frankfurt am Main (EXC 115)
- Mike Heilemann
- Ivan Dikic
LOEWE programme (Network Ub-Net)
- Ivan Dikic
LOEWE Center for Gene and Cell Therapy Frankfurt (CGT)
- Ivan Dikic
7.FP, COFUND, Goethe International Postdoc Program GO-IN (No 291776)
- Paolo Grumati
SNF Sinergia (CRSII#_154421)
- Fulvio Reggiori
ZonMw (VICI (016.130.606))
- Fulvio Reggiori
Marie Sklodowska-Curie Cofund
- Fulvio Reggiori
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Grumati 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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Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy
eLife 6:e25555.
https://doi.org/10.7554/eLife.25555
Further reading
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- Biochemistry and Chemical Biology
- Microbiology and Infectious Disease
Teichoic acids (TA) are linear phospho-saccharidic polymers and important constituents of the cell envelope of Gram-positive bacteria, either bound to the peptidoglycan as wall teichoic acids (WTA) or to the membrane as lipoteichoic acids (LTA). The composition of TA varies greatly but the presence of both WTA and LTA is highly conserved, hinting at an underlying fundamental function that is distinct from their specific roles in diverse organisms. We report the observation of a periplasmic space in Streptococcus pneumoniae by cryo-electron microscopy of vitreous sections. The thickness and appearance of this region change upon deletion of genes involved in the attachment of TA, supporting their role in the maintenance of a periplasmic space in Gram-positive bacteria as a possible universal function. Consequences of these mutations were further examined by super-resolved microscopy, following metabolic labeling and fluorophore coupling by click chemistry. This novel labeling method also enabled in-gel analysis of cell fractions. With this approach, we were able to titrate the actual amount of TA per cell and to determine the ratio of WTA to LTA. In addition, we followed the change of TA length during growth phases, and discovered that a mutant devoid of LTA accumulates the membrane-bound polymerized TA precursor.
