Atlastin 2/3 regulate ER targeting of the ULK1 complex to initiate autophagy
© 2021 Liu et al..
Dynamic targeting of the ULK1 complex to the ER is crucial for initiating autophagosome formation and for subsequent formation of ER-isolation membrane (IM; autophagosomal precursor) contact during IM expansion. Little is known about how the ULK1 complex, which comprises FIP200, ULK1, ATG13, and ATG101 and does not exist as a constitutively coassembled complex, is recruited and stabilized on the ER. Here, we demonstrate that the ER-localized transmembrane proteins Atlastin 2 and 3 (ATL2/3) contribute to recruitment and stabilization of ULK1 and ATG101 at the FIP200-ATG13-specified autophagosome formation sites on the ER. In ATL2/3 KO cells, formation of FIP200 and ATG13 puncta is unaffected, while targeting of ULK1 and ATG101 is severely impaired. Consequently, IM initiation is compromised and slowed. ATL2/3 directly interact with ULK1 and ATG13 and facilitate the ATG13-mediated recruitment/stabilization of ULK1 and ATG101. ATL2/3 also participate in forming ER-IM tethering complexes. Our study provides insights into the dynamic assembly of the ULK1 complex on the ER for autophagosome formation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:220 |
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| Enthalten in: |
The Journal of cell biology - 220(2021), 7 vom: 05. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Nan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.10.2021 Date Revised 13.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1083/jcb.202012091 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM325400350 |
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| 100 | 1 | |a Liu, Nan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Atlastin 2/3 regulate ER targeting of the ULK1 complex to initiate autophagy |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 06.10.2021 | ||
| 500 | |a Date Revised 13.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 Liu et al. | ||
| 520 | |a Dynamic targeting of the ULK1 complex to the ER is crucial for initiating autophagosome formation and for subsequent formation of ER-isolation membrane (IM; autophagosomal precursor) contact during IM expansion. Little is known about how the ULK1 complex, which comprises FIP200, ULK1, ATG13, and ATG101 and does not exist as a constitutively coassembled complex, is recruited and stabilized on the ER. Here, we demonstrate that the ER-localized transmembrane proteins Atlastin 2 and 3 (ATL2/3) contribute to recruitment and stabilization of ULK1 and ATG101 at the FIP200-ATG13-specified autophagosome formation sites on the ER. In ATL2/3 KO cells, formation of FIP200 and ATG13 puncta is unaffected, while targeting of ULK1 and ATG101 is severely impaired. Consequently, IM initiation is compromised and slowed. ATL2/3 directly interact with ULK1 and ATG13 and facilitate the ATG13-mediated recruitment/stabilization of ULK1 and ATG101. ATL2/3 also participate in forming ER-IM tethering complexes. Our study provides insights into the dynamic assembly of the ULK1 complex on the ER for autophagosome formation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a ATG13 protein, human |2 NLM | |
| 650 | 7 | |a ATG101 protein, human |2 NLM | |
| 650 | 7 | |a Autophagy-Related Proteins |2 NLM | |
| 650 | 7 | |a Intracellular Signaling Peptides and Proteins |2 NLM | |
| 650 | 7 | |a Multiprotein Complexes |2 NLM | |
| 650 | 7 | |a RB1CC1 protein, human |2 NLM | |
| 650 | 7 | |a Vesicular Transport Proteins |2 NLM | |
| 650 | 7 | |a Autophagy-Related Protein-1 Homolog |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a ULK1 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a ATL2 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.6.1.- |2 NLM | |
| 650 | 7 | |a GTP Phosphohydrolases |2 NLM | |
| 650 | 7 | |a EC 3.6.1.- |2 NLM | |
| 650 | 7 | |a ATL3 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.6.5.- |2 NLM | |
| 700 | 1 | |a Zhao, Hongyu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yan G |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Junjie |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hong |e verfasserin |4 aut | |
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