English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
Add to Basket
  Local TagsRelease HistoryDetailsSummary

Released
Journal Article

Heteromeric clusters of ubiquitinated ER-shaping proteins drive ER-phagy

MPS-Authors
/persons/resource/persons194665

Bhaskara,  Ramachandra M.       
Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt am Main, Germany;
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society;
Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt am Main, Germany;

/persons/resource/persons15259

Hummer,  Gerhard       
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society;
Institute of Biophysics, Goethe University Frankfurt, Frankfurt am Main, Germany;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)

s41586-023-06090-9.pdf
(Any fulltext), 14MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Foronda, H., Fu, Y., Covarrubias-Pinto, A., Bocker, H. T., González, A., Seemann, E., et al. (2023). Heteromeric clusters of ubiquitinated ER-shaping proteins drive ER-phagy. Nature, 618(7964), 402-410. doi:10.1038/s41586-023-06090-9.


Cite as: https://hdl.handle.net/21.11116/0000-000D-3376-5
Abstract
Membrane-shaping proteins characterized by reticulon homology domains play an important part in the dynamic remodelling of the endoplasmic reticulum (ER). An example of such a protein is FAM134B, which can bind LC3 proteins and mediate the degradation of ER sheets through selective autophagy (ER-phagy)1. Mutations in FAM134B result in a neurodegenerative disorder in humans that mainly affects sensory and autonomic neurons2. Here we report that ARL6IP1, another ER-shaping protein that contains a reticulon homology domain and is associated with sensory loss3, interacts with FAM134B and participates in the formation of heteromeric multi-protein clusters required for ER-phagy. Moreover, ubiquitination of ARL6IP1 promotes this process. Accordingly, disruption of Arl6ip1 in mice causes an expansion of ER sheets in sensory neurons that degenerate over time. Primary cells obtained from Arl6ip1-deficient mice or from patients display incomplete budding of ER membranes and severe impairment of ER-phagy flux. Therefore, we propose that the clustering of ubiquitinated ER-shaping proteins facilitates the dynamic remodelling of the ER during ER-phagy and is important for neuronal maintenance.