Evidence map›Paper›PMID 28954816›Full record

ArticleMolecular pharmacology2017

Effective Attenuation of Adenosine A1R Signaling by Neurabin Requires Oligomerization of Neurabin.

Yunjia Chen, Christopher Booth, Hongxia Wang, Raymond X Wang, Dimitra Terzi, Venetia Zachariou, Kai Jiao, Jin Zhang, Qin Wang

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

Article in Molecular pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 41% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Article
  3. 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.

Yunjia ChenDepartments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York (D.T., V.Z.).
Christopher BoothDepartments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York (D.T., V.Z.).
Hongxia WangDepartments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York (D.T., V.Z.).
Raymond X WangDepartments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York (D.T., V.Z.).
Dimitra TerziDepartments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York (D.T., V.Z.).
Venetia ZachariouDepartments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York (D.T., V.Z.).
Kai JiaoDepartments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York (D.T., V.Z.).
Jin ZhangDepartments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York (D.T., V.Z.).
Qin WangDepartments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York (D.T., V.Z.) qinwang@uab.edu.
University of California, San Diego · USIcahn School of Medicine at Mount Sinai · USUniversity of Alabama at Birmingham · US

Funding

Cellular Mechanisms of Antidepressant Drug Actions in Neuropathic Pain ModelsR01NS086444 · NINDS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ZACHARIOU, VENETIA · 2014 to 2023
$4.4M
Regulation of novel alpha2A adrenergic receptor signaling by spinophilinR01MH081917 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI WANG, QIN · 2009 to 2019
$3.9M
Targeting HDAC6 for the treatment of neuropathic painR21NS098264 · NINDS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ZACHARIOU, VENETIA · 2017 to 2018
$466k
NIMH NIH HHS R01 MH081917NINDS NIH HHS R01 NS086444NINDS NIH HHS R21 NS098264
6 · The paper itself

Abstract

The adenosine A1 receptor (A1R) is a key mediator of the neuroprotective effect by endogenous adenosine. Yet targeting this receptor for neuroprotection is challenging due to its broad expression throughout the body. A mechanistic understanding of the regulation of A1R signaling is necessary for the future design of therapeutic agents that can selectively enhance A1R-mediated responses in the nervous system. In this study, we demonstrate that A1R activation leads to a sustained localization of regulator of G protein signaling 4 (RGS4) at the plasma membrane, a process that requires neurabin (a neural tissue-specific protein). A1R and RGS4 interact with the overlapping regions of neurabin. In addition, neurabin domains required for oligomerization are essential for formation of the A1R/neurabin/RGS4 ternary complex, as well as for stable localization of RGS4 at the plasma membrane and attenuation of A1R signaling. Thus, A1R and RGS4 each likely interact with one neurabin molecule in a neurabin homo-oligomer to form a ternary complex, representing a novel mode of regulation of G protein-coupled receptor signaling by scaffolding proteins. Our mechanistic analysis of neurabin-mediated regulation of A1R signaling in this study will be valuable for the future design of therapeutic agents that can selectively enhance A1R-mediated responses in the nervous system.

Indexed as

AnimalsCell MembraneChlorocebus aethiopsCOS CellsHEK293 CellsHumansMicrofilament ProteinsMultiprotein ComplexesNerve Tissue ProteinsNeurabinsProtein DomainsProtein MultimerizationProtein TransportReceptor, Adenosine A1RGS ProteinsSignal TransductionMicrofilament ProteinsMultiprotein ComplexesNerve Tissue ProteinsNeurabinsReceptor, Adenosine A1RGS4 proteinRGS Proteins

Identifiers

PMID28954816
PMCPMC5676298
OpenAlexW2758066145

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.