Evidence map›Paper›PMID 25056953›Full record

ArticleThe Journal of biological chemistry2014

The duplicated α7 subunits assemble and form functional nicotinic receptors with the full-length α7.

Ying Wang, Cheng Xiao, Tim Indersmitten, Robert Freedman, Sherry Leonard, Henry A Lester

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 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

52 citing papers in PubMed, 91 citations in OpenAlex.

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  8. Human restrictedFrontiers in neuroscience · 2024
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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 2 institutions in 1 country.

Ying WangDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125 and.
Cheng XiaoDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125 and.
Tim IndersmittenDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125 and.
Robert FreedmanDepartment of Psychiatry, University of Colorado at Denver, Denver, Colorado 80045.
Sherry LeonardDepartment of Psychiatry, University of Colorado at Denver, Denver, Colorado 80045.
Henry A LesterDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125 and. Electronic address: lester@caltech.edu.
California Institute of Technology · USUniversity of Colorado Denver · US

Funding

Avermectin Receptors for Neuronal EngineeringRC1MH088550 · NIMH · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI LESTER, HENRY A. · 2009 to 2010
$656k
NIMH NIH HHS MH088550NIMH NIH HHS RC1 MH088550
6 · The paper itself

Abstract

The α7 nicotinic acetylcholine receptor gene (CHRNA7) is linked to schizophrenia. A partial duplication of CHRNA7 (CHRFAM7A) is found in humans on 15q13-14. Exon 6 of CHRFAM7A harbors a 2-bp deletion polymorphism, CHRFAM7AΔ2bp, which is also associated with schizophrenia. To understand the effects of the duplicated subunits on α7 receptors, we fused α7, dupα7, and dupΔα7 subunits with various fluorescent proteins. The duplicated subunits co-localized with full-length α7 subunits in mouse neuroblastoma cells (Neuro2a) as well as rat hippocampal neurons. We investigated the interaction between the duplicated subunits and full-length α7 by measuring Förster resonance energy transfer using donor recovery after photobleaching and fluorescence lifetime imaging microscopy. The results revealed that the duplicated proteins co-assemble with α7. In electrophysiological studies, Leu at the 9'-position in the M2 membrane-spanning segment was replaced with Cys in dupα7 or dupΔα7, and constructs were co-transfected with full-length α7 in Neuro2a cells. Exposure to ethylammonium methanethiosulfonate inhibited acetylcholine-induced currents, showing that the assembled functional nicotinic acetylcholine receptors (nAChRs) included the duplicated subunit. Incorporation of dupα7 and dupΔα7 subunits modestly changes the sensitivity of receptors to choline and varenicline. Thus, the duplicated proteins are assembled and transported to the cell membrane together with full-length α7 subunits and alter the function of the nAChRs. The characterization of dupα7 and dupΔα7 as well as their influence on α7 nAChRs may help explain the pathophysiology of schizophrenia and may suggest therapeutic strategies.

Indexed as

Acetylcholinealpha7 Nicotinic Acetylcholine ReceptorAnimalsBenzazepinesCell Line, TumorCholineGene DuplicationHumansMembrane PotentialsMiceNicotinic AgonistsProtein MultimerizationProtein Structure, QuaternaryProtein SubunitsProtein TransportQuinoxalinesAcetylcholinealpha7 Nicotinic Acetylcholine ReceptorBenzazepinesCholineNicotinic AgonistsProtein SubunitsQuinoxalinesVareniclineCholineElectrophysiologyFluorescence Recovery after Photobleaching (FRAP)Fluorescence Resonance Energy Transfer (FRET)GenomicsIon ChannelLigand-gated ChannelNicotinic Acetylcholine Receptors (nAChR)Patch ClampSchizophrenia

Identifiers

PMID25056953
PMCPMC4176222
OpenAlexW2003298566

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.