Evidence map›Paper›PMID 27445338›Full record

ArticleThe Journal of biological chemistry2016

Ubiquitin-specific Protease 36 (USP36) Controls Neuronal Precursor Cell-expressed Developmentally Down-regulated 4-2 (Nedd4-2) Actions over the Neurotrophin Receptor TrkA and Potassium Voltage-gated Channels 7.2/3 (Kv7.2/3).

Begoña Anta, Carlos Martín-Rodríguez, Carolina Gomis-Perez, Laura Calvo, Saray López-Benito, Andrés A Calderón-García, Cristina Vicente-García, Álvaro Villarroel, Juan C Arévalo

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.2field-weighted citation impact, top 35% 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

8 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
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

9 authors at 3 institutions in 1 country.

Begoña AntaFrom the Departmento de Biología Celular y Patología, Instituto de Neurociencias de Castilla y León, University of Salamanca, Salamanca 37007, Spain, the Institute of Biomedical Research of Salamanca, 47195 Salamanca, Spain, and.
Carlos Martín-RodríguezFrom the Departmento de Biología Celular y Patología, Instituto de Neurociencias de Castilla y León, University of Salamanca, Salamanca 37007, Spain, the Institute of Biomedical Research of Salamanca, 47195 Salamanca, Spain, and.
Carolina Gomis-Perezthe Unidad de Biofísica, Consejo Superior de Investigaciones Científicas, CSIC, UPV/EHU, Universidad del País Vasco, barrio Sarriena s/n, 48940 Leoia, Spain.
Laura CalvoFrom the Departmento de Biología Celular y Patología, Instituto de Neurociencias de Castilla y León, University of Salamanca, Salamanca 37007, Spain, the Institute of Biomedical Research of Salamanca, 47195 Salamanca, Spain, and.
Saray López-BenitoFrom the Departmento de Biología Celular y Patología, Instituto de Neurociencias de Castilla y León, University of Salamanca, Salamanca 37007, Spain, the Institute of Biomedical Research of Salamanca, 47195 Salamanca, Spain, and.
Andrés A Calderón-GarcíaFrom the Departmento de Biología Celular y Patología, Instituto de Neurociencias de Castilla y León, University of Salamanca, Salamanca 37007, Spain.
Cristina Vicente-GarcíaFrom the Departmento de Biología Celular y Patología, Instituto de Neurociencias de Castilla y León, University of Salamanca, Salamanca 37007, Spain, the Institute of Biomedical Research of Salamanca, 47195 Salamanca, Spain, and.
Álvaro Villarroelthe Unidad de Biofísica, Consejo Superior de Investigaciones Científicas, CSIC, UPV/EHU, Universidad del País Vasco, barrio Sarriena s/n, 48940 Leoia, Spain.
Juan C ArévaloFrom the Departmento de Biología Celular y Patología, Instituto de Neurociencias de Castilla y León, University of Salamanca, Salamanca 37007, Spain, the Institute of Biomedical Research of Salamanca, 47195 Salamanca, Spain, and arevalojc@usal.es.
Universidad de Salamanca · ESInstituto de Estudios de Ciencias de la Salud de Castilla y León · ESConsejo Superior de Investigaciones Científicas · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ubiquitination of the TrkA neurotrophin receptor in response to NGF is critical in the regulation of TrkA activation and functions. TrkA is ubiquitinated, among other E3 ubiquitin ligases, by Nedd4-2. To understand mechanistically how TrkA ubiquitination is regulated, we performed a siRNA screening to identify deubiquitinating enzymes and found that USP36 acts as an important regulator of TrkA activation kinetics and ubiquitination. However, USP36 action on TrkA was indirect because it does not deubiquitinate TrkA. Instead, USP36 binds to Nedd4-2 and regulates the association of TrkA and Nedd4-2. In addition, depletion of USP36 increases TrkA·Nedd4-2 complex formation, whereas USP36 expression disrupts the complex, resulting in an enhancement or impairment of Nedd4-2-dependent TrkA ubiquitination, respectively. Moreover, USP36 depletion leads to enhanced total and surface TrkA expression that results in increased NGF-mediated TrkA activation and signaling that augments PC12 cell differentiation. USP36 actions extend beyond TrkA because the presence of USP36 interferes with Nedd4-2-dependent Kv7.2/3 channel regulation. Our results demonstrate that USP36 binds to and regulates the actions of Nedd4-2 over different substrates affecting their expression and functions.

Indexed as

AnimalsCell DifferentiationEndosomal Sorting Complexes Required for TransportGene Expression RegulationHEK293 CellsHumansKCNQ2 Potassium ChannelKCNQ3 Potassium ChannelMiceNedd4 Ubiquitin Protein LigasesNeural Stem CellsPC12 CellsProtein BindingRatsReceptor, trkAUbiquitin-Protein LigasesEndosomal Sorting Complexes Required for TransportKCNQ2 Potassium ChannelKCNQ3 Potassium ChannelNedd4L protein, humanNedd4l protein, mouseNEDD4L protein, ratNedd4 protein, humanNedd4 protein, ratNedd4 Ubiquitin Protein LigasesNTRK1 protein, humanReceptor, trkAUbiquitin-Protein LigasesUbiquitin ThiolesteraseUSP36 protein, humandeubiquitylation (deubiquitination)Kv channelsNedd4-2neurite outgrowthneurotrophic factorneurotrophinTrkAubiquitylation (ubiquitination)USP36

Identifiers

PMID27445338
PMCPMC5009282
OpenAlexW2498807958

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.