ArticleThe Journal of biological chemistry2014
The WD40-repeat proteins WDR-20 and WDR-48 bind and activate the deubiquitinating enzyme USP-46 to promote the abundance of the glutamate receptor GLR-1 in the ventral nerve cord of Caenorhabditis elegans.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- The Emerging Roles of E3 Ligases and DUBs in Neurodegenerative Diseases.Molecular neurobiology · 2023Pooled it
- Autophagy-Independent Function of ATG-18 Is Essential for Gonadal Longevity in Caenorhabditis elegans.Aging cell · 2026Article
- Structure-activity relationship of ginsenoside derivatives with different glycosides and double bond position on anti-aging bioactivities.Journal of ginseng research · 2025Article
- DEPDC5 regulates the strength of excitatory synaptic transmission by interacting with ubiquitin-specific protease 46.Neurobiology of disease · 2025Article
- Pseudokinase TRIB3 stabilizes SSRP1 via USP10-mediated deubiquitination to promote multiple myeloma progression.Oncogene · 2025Article
- The deubiquitinase cofactor UAF1 interacts with USP1 and plays an essential role in spermiogenesis.iScience · 2024Article
- Structure, Inhibitors, and Biological Function in Nervous System and Cancer of Ubiquitin-Specific Protease 46.Bioinformatics and biology insights · 2024Review
- The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6.Nature communications · 2023Article
- The USP46 complex deubiquitylates LRP6 to promote Wnt/β-catenin signaling.Nature communications · 2023Article
- Spotlights on ubiquitin-specific protease 12 (USP12) in diseases: from multifaceted roles to pathophysiological mechanisms.Journal of translational medicine · 2023Review
- Article
- A Fiji process for quantifying fluorescent puncta in linear cellular structures.microPublication biology · 2023Article
- HPVE6-USP46 Mediated Cdt2 Stabilization Reduces Set8 Mediated H4K20-Methylation to Induce Gene Expression Changes.Cancers · 2021Article
- The WD40-Repeat Protein WDR-20 and the Deubiquitinating Enzyme USP-46 Promote Cell Surface Levels of Glutamate Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Structural basis of FANCD2 deubiquitination by USP1-UAF1.Nature structural & molecular biology · 2021Article
- Deubiquitylating enzymes in neuronal health and disease.Cell death & disease · 2021Review
- Article
- Student Annotations of Published Data as a Collaboration between an Online Laboratory Course and the C. elegans Database, WormBase.Journal of microbiology & biology education · 2021Article
- Mutations in two ERAD E3 ubiquitin ligase enzymes reduce spontaneous reversal frequency inmicroPublication biology · 2020Article
- The WD40-repeat protein WDR-48 promotes the stability of the deubiquitinating enzyme USP-46 by inhibiting its ubiquitination and degradation.The Journal of biological chemistry · 2020Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
Ubiquitin-mediated endocytosis and degradation of glutamate receptors controls their synaptic abundance and is implicated in modulating synaptic strength. The deubiquitinating enzymes (DUBs) that function in the nervous system are beginning to be defined, but the mechanisms that control DUB activity in vivo are understood poorly. We found previously that the DUB USP-46 deubiquitinates the Caenorhabditis elegans glutamate receptor GLR-1 and prevents its degradation in the lysosome. The WD40-repeat (WDR) proteins WDR20 and WDR48/UAF1 have been shown to bind to USP46 and stimulate its catalytic activity in other systems. Here we identify the C. elegans homologs of these WDR proteins and show that C. elegans WDR-20 and WDR-48 can bind and stimulate USP-46 catalytic activity in vitro. Overexpression of these activator proteins in vivo increases the abundance of GLR-1 in the ventral nerve cord, and this effect is further enhanced by coexpression of USP-46. Biochemical characterization indicates that this increase in GLR-1 abundance correlates with decreased levels of ubiquitin-GLR-1 conjugates, suggesting that WDR-20, WDR-48, and USP-46 function together to deubiquitinate and stabilize GLR-1 in neurons. Overexpression of WDR-20 and WDR-48 results in alterations in locomotion behavior consistent with increased glutamatergic signaling, and this effect is blocked in usp-46 loss-of-function mutants. Conversely, wdr-20 and wdr-48 loss-of-function mutants exhibit changes in locomotion behavior that are consistent with decreased glutamatergic signaling. We propose that WDR-20 and WDR-48 form a complex with USP-46 and stimulate the DUB to deubiquitinate and stabilize GLR-1 in vivo.
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