Heteromeric clusters of ubiquitinated ER-shaping proteins drive ER-phagy
© 2023. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:618 |
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| Enthalten in: |
Nature - 618(2023), 7964 vom: 24. Juni, Seite 402-410 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Foronda, Hector [VerfasserIn] |
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| Links: |
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| Themen: |
ARL6IP1 protein, human |
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| Anmerkungen: |
Date Completed 13.06.2023 Date Revised 13.06.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41586-023-06090-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357283775 |
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| 100 | 1 | |a Foronda, Hector |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Heteromeric clusters of ubiquitinated ER-shaping proteins drive ER-phagy |
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| 500 | |a Date Revised 13.06.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Intracellular Signaling Peptides and Proteins |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a Ubiquitinated Proteins |2 NLM | |
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| 650 | 7 | |a Fam134b protein, mouse |2 NLM | |
| 650 | 7 | |a Arl6ip1 protein, mouse |2 NLM | |
| 650 | 7 | |a ARL6IP1 protein, human |2 NLM | |
| 700 | 1 | |a Fu, Yangxue |e verfasserin |4 aut | |
| 700 | 1 | |a Covarrubias-Pinto, Adriana |e verfasserin |4 aut | |
| 700 | 1 | |a Bocker, Hartmut T |e verfasserin |4 aut | |
| 700 | 1 | |a González, Alexis |e verfasserin |4 aut | |
| 700 | 1 | |a Seemann, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Franzka, Patricia |e verfasserin |4 aut | |
| 700 | 1 | |a Bock, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Bhaskara, Ramachandra M |e verfasserin |4 aut | |
| 700 | 1 | |a Liebmann, Lutz |e verfasserin |4 aut | |
| 700 | 1 | |a Hoffmann, Marina E |e verfasserin |4 aut | |
| 700 | 1 | |a Katona, Istvan |e verfasserin |4 aut | |
| 700 | 1 | |a Koch, Nicole |e verfasserin |4 aut | |
| 700 | 1 | |a Weis, Joachim |e verfasserin |4 aut | |
| 700 | 1 | |a Kurth, Ingo |e verfasserin |4 aut | |
| 700 | 1 | |a Gleeson, Joseph G |e verfasserin |4 aut | |
| 700 | 1 | |a Reggiori, Fulvio |e verfasserin |4 aut | |
| 700 | 1 | |a Hummer, Gerhard |e verfasserin |4 aut | |
| 700 | 1 | |a Kessels, Michael M |e verfasserin |4 aut | |
| 700 | 1 | |a Qualmann, Britta |e verfasserin |4 aut | |
| 700 | 1 | |a Mari, Muriel |e verfasserin |4 aut | |
| 700 | 1 | |a Dikić, Ivan |e verfasserin |4 aut | |
| 700 | 1 | |a Hübner, Christian A |e verfasserin |4 aut | |
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