Ubiquitylation of the ER-Shaping Protein Lunapark via the CRL3KLHL12 Ubiquitin Ligase Complex
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved..
Cullin-RING ligases (CRLs) control key cellular processes by promoting ubiquitylation of a multitude of soluble cytosolic and nuclear proteins. Subsets of CRL complexes are recruited and activated locally at cellular membranes; however, few CRL functions and substrates at these distinct cellular compartments are known. Here, we use a proteomic screen to identify proteins that are ubiquitylated at cellular membranes and found that Lunapark, an endoplasmic reticulum (ER)-shaping protein localized to ER three-way junctions, is ubiquitylated by the CRL3KLHL12 ubiquitin ligase. We demonstrate that Lunapark interacts with mechanistic target of rapamycin complex-1 (mTORC1), a central cellular regulator that coordinates growth and metabolism with environmental conditions. We show that mTORC1 binds Lunapark specifically at three-way junctions, and lysosomes, where mTORC1 is activated, make contact with three-way junctions where Lunapark resides. Inhibition of Lunapark ubiquitylation results in neurodevelopmental defects indicating that KLHL12-dependent ubiquitylation of Lunapark is required for normal growth and development.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
Cell reports - 31(2020), 7 vom: 19. Mai, Seite 107664 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yuniati, Laurensia [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.05.2021 Date Revised 21.05.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2020.107664 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM310163056 |
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| 100 | 1 | |a Yuniati, Laurensia |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Ubiquitylation of the ER-Shaping Protein Lunapark via the CRL3KLHL12 Ubiquitin Ligase Complex |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Revised 21.05.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Cullin-RING ligases (CRLs) control key cellular processes by promoting ubiquitylation of a multitude of soluble cytosolic and nuclear proteins. Subsets of CRL complexes are recruited and activated locally at cellular membranes; however, few CRL functions and substrates at these distinct cellular compartments are known. Here, we use a proteomic screen to identify proteins that are ubiquitylated at cellular membranes and found that Lunapark, an endoplasmic reticulum (ER)-shaping protein localized to ER three-way junctions, is ubiquitylated by the CRL3KLHL12 ubiquitin ligase. We demonstrate that Lunapark interacts with mechanistic target of rapamycin complex-1 (mTORC1), a central cellular regulator that coordinates growth and metabolism with environmental conditions. We show that mTORC1 binds Lunapark specifically at three-way junctions, and lysosomes, where mTORC1 is activated, make contact with three-way junctions where Lunapark resides. Inhibition of Lunapark ubiquitylation results in neurodevelopmental defects indicating that KLHL12-dependent ubiquitylation of Lunapark is required for normal growth and development | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ER three-way junction | |
| 650 | 4 | |a Lunapark | |
| 650 | 4 | |a cullin-RING ligases | |
| 650 | 4 | |a endoplasmic reticulum | |
| 650 | 4 | |a lysosome | |
| 650 | 4 | |a mTORC1 | |
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| 650 | 7 | |a KLHL12 protein, human |2 NLM | |
| 650 | 7 | |a LNPK protein, human |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a Ubiquitin-Protein Ligases |2 NLM | |
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| 650 | 7 | |a Mechanistic Target of Rapamycin Complex 1 |2 NLM | |
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| 700 | 1 | |a Lauriola, Angela |e verfasserin |4 aut | |
| 700 | 1 | |a Gerritsen, Manouk |e verfasserin |4 aut | |
| 700 | 1 | |a Abreu, Susana |e verfasserin |4 aut | |
| 700 | 1 | |a Ni, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Tesoriero, Chiara |e verfasserin |4 aut | |
| 700 | 1 | |a Onireti, Jacob O |e verfasserin |4 aut | |
| 700 | 1 | |a Low, Teck Yew |e verfasserin |4 aut | |
| 700 | 1 | |a Heck, Albert J R |e verfasserin |4 aut | |
| 700 | 1 | |a Vettori, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Cardozo, Timothy |e verfasserin |4 aut | |
| 700 | 1 | |a Guardavaccaro, Daniele |e verfasserin |4 aut | |
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