PUBLICATION
Ubiquitylation of the ER-Shaping Protein Lunapark via the CRL3KLHL12 Ubiquitin Ligase Complex
- Authors
- Yuniati, L., Lauriola, A., Gerritsen, M., Abreu, S., Ni, E., Tesoriero, C., Onireti, J.O., Low, T.Y., Heck, A.J.R., Vettori, A., Cardozo, T., Guardavaccaro, D.
- ID
- ZDB-PUB-210522-9
- Date
- 2020
- Source
- Cell Reports 31: 107664 (Journal)
- Registered Authors
- Vettori, Andrea
- Keywords
- ER three-way junction, Lunapark, cullin-RING ligases, endoplasmic reticulum, lysosome, mTORC1, ubiquitin
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing/metabolism*
- Animals
- Animals, Genetically Modified
- Cell Line, Tumor
- Cullin Proteins/metabolism*
- Endoplasmic Reticulum/metabolism*
- HEK293 Cells
- Humans
- Mechanistic Target of Rapamycin Complex 1/metabolism
- Membrane Proteins/metabolism*
- Ubiquitin-Protein Ligases/metabolism*
- Ubiquitination
- Zebrafish
- PubMed
- 32433973 Full text @ Cell Rep.
Citation
Yuniati, L., Lauriola, A., Gerritsen, M., Abreu, S., Ni, E., Tesoriero, C., Onireti, J.O., Low, T.Y., Heck, A.J.R., Vettori, A., Cardozo, T., Guardavaccaro, D. (2020) Ubiquitylation of the ER-Shaping Protein Lunapark via the CRL3KLHL12 Ubiquitin Ligase Complex. Cell Reports. 31:107664.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping