Evidence map›Paper›PMID 25193658›Full record

ArticleThe Journal of biological chemistry2014

Ring finger protein 34 (RNF34) interacts with and promotes γ-aminobutyric acid type-A receptor degradation via ubiquitination of the γ2 subunit.

Hongbing Jin, Tzu-Ting Chiou, David R Serwanski, Celia P Miralles, Noelia Pinal, Angel L De Blas

Open access · hybridAbstract read
In one paragraph

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 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.1field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 32 citations in OpenAlex.

  1. GABASynapse (New York, N.Y.) · 2026
    Review
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  3. Proteostasis regulation of GABABiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025
    Review
  4. Review
  5. Article
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  7. Article
  8. Article
  9. Article
  10. Article
  11. Expression of protocadherin-γC4 protein in the rat brain.The Journal of comparative neurology · 2020
    Article
  12. Article
  13. Diazepam Accelerates GABAFrontiers in cellular neuroscience · 2019
    Article
  14. Review
  15. γ2 GABAFrontiers in cellular neuroscience · 2018
    Review
  16. Influence ofFrontiers in aging neuroscience · 2018
    Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Hongbing JinFrom the Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269.
Tzu-Ting ChiouFrom the Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269.
David R SerwanskiFrom the Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269.
Celia P MirallesFrom the Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269.
Noelia PinalFrom the Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269.
Angel L De BlasFrom the Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269 angel.deblas@uconn.edu.
University of Connecticut · US

Funding

GABAA RECEPTOR - INTERACTING PROTEINSR01NS038752 · NINDS · UNIVERSITY OF CONNECTICUT STORRS · PI DE BLAS, ANGEL L · 2000 to 2014
$4.1M
NINDS NIH HHS R01 NS038752NINDS NIH HHS R01NS038752
6 · The paper itself

Abstract

We have found that the large intracellular loop of the γ2 GABAA receptor (R) subunit (γ2IL) interacts with RNF34 (an E3 ubiquitin ligase), as shown by yeast two-hybrid and in vitro pulldown assays. In brain extracts, RNF34 co-immunoprecipitates with assembled GABAARs. In co-transfected HEK293 cells, RNF34 reduces the expression of the γ2 GABAAR subunit by increasing the ratio of ubiquitinated/nonubiquitinated γ2. Mutating several lysines of the γ2IL into arginines makes the γ2 subunit resistant to RNF34-induced degradation. RNF34 also reduces the expression of the γ2 subunit when α1 and β3 subunits are co-assembled with γ2. This effect is partially reversed by leupeptin or MG132, indicating that both the lysosomal and proteasomal degradation pathways are involved. Immunofluorescence of cultured hippocampal neurons shows that RNF34 forms clusters and that a subset of these clusters is associated with GABAergic synapses. This association is also observed in the intact rat brain by electron microscopy immunocytochemistry. RNF34 is not expressed until the 2nd postnatal week of rat brain development, being highly expressed in some interneurons. Overexpression of RNF34 in hippocampal neurons decreases the density of γ2 GABAAR clusters and the number of GABAergic contacts that these neurons receive. Knocking down endogenous RNF34 with shRNA leads to increased γ2 GABAAR cluster density and GABAergic innervation. The results indicate that RNF34 regulates postsynaptic γ2-GABAAR clustering and GABAergic synaptic innervation by interacting with and ubiquitinating the γ2-GABAAR subunit promoting GABAAR degradation.

Indexed as

AnimalsBrainCarrier ProteinsGene Expression RegulationGuinea PigsHEK293 CellsHippocampusHumansLysosomesNeuronsProteasome Endopeptidase ComplexProtein BindingProtein TransportRatsReceptors, GABA-BSynapsesCarrier ProteinsGabbr2 protein, ratProteasome Endopeptidase ComplexReceptors, GABA-BRNF34 protein, humanUbiquitinE3 Ubiquitin LigaseGABAA ReceptorsInteractionLysosomeProteasomeRNF34SynapseUbiquitinationYeast Two-hybrid

Identifiers

PMID25193658
PMCPMC4200290
OpenAlexW2083676602

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.