Evidence map›Paper›PMID 29940568›Full record

ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2018

Gαi Proteins are Indispensable for Hearing.

Sandra Beer-Hammer, Sze Chim Lee, Stephanie A Mauriac, Veronika Leiss, Isabel A M Groh, Ana Novakovic, Roland P Piekorz, Kirsten Bucher, Chengfang Chen, Kun Ni and 11 more

Open access · goldAbstract read
In one paragraph

Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.9field-weighted citation impact, top 16% 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

27 citing papers in PubMed, 38 citations in OpenAlex.

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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

21 authors at 7 institutions in 6 countries.

Sandra Beer-HammerDepartment of Pharmacology and Experimental Therapy, and Interfaculty Center of Pharmacogenomics and Drug Research (ICePhA), University of Tübingen, Tübingen, Germany.
Sze Chim LeeMolecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, University of Tübingen, Tübingen, Germany.
Stephanie A MauriacINSERM, Neurocentre Magendie, U1215, 146 rue Leo-Saignat, Bordeaux, France.
Veronika LeissDepartment of Pharmacology and Experimental Therapy, and Interfaculty Center of Pharmacogenomics and Drug Research (ICePhA), University of Tübingen, Tübingen, Germany.
Isabel A M GrohDepartment of Pharmacology and Experimental Therapy, and Interfaculty Center of Pharmacogenomics and Drug Research (ICePhA), University of Tübingen, Tübingen, Germany.
Ana NovakovicDepartment of Pharmacology and Experimental Therapy, and Interfaculty Center of Pharmacogenomics and Drug Research (ICePhA), University of Tübingen, Tübingen, Germany.
Roland P PiekorzInstitute for Biochemistry and Molecular Biology II, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany.
Kirsten BucherDepartment of Pharmacology and Experimental Therapy, and Interfaculty Center of Pharmacogenomics and Drug Research (ICePhA), University of Tübingen, Tübingen, Germany.
Chengfang ChenMolecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, University of Tübingen, Tübingen, Germany.
Kun NiMolecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, University of Tübingen, Tübingen, Germany.
Wibke SingerMolecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, University of Tübingen, Tübingen, Germany.
Csaba HarasztosiDepartment of Otolaryngology, Tübingen Hearing Research Center, Section of Physiological Acoustics and Communication, University of Tübingen, Tübingen, Germany.
Thomas SchimmangInstituto de Biologíay Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, Valladolid, Spain.
Ulrike ZimmermannMolecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, University of Tübingen, Tübingen, Germany.
Klaus PfefferInstitute of Medical Microbiology and Hospital Hygiene, University of Düsseldorf, Düsseldorf, Germany.
Lutz BirnbaumerNeurobiology Laboratory, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina, USA.
Andrew ForgeUCL Ear Institute, London, United Kingdom.
Mireille MontcouquiolINSERM, Neurocentre Magendie, U1215, 146 rue Leo-Saignat, Bordeaux, France.
Marlies KnipperMolecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, University of Tübingen, Tübingen, Germany.
Bernd NürnbergDepartment of Pharmacology and Experimental Therapy, and Interfaculty Center of Pharmacogenomics and Drug Research (ICePhA), University of Tübingen, Tübingen, Germany.
Lukas RüttigerMolecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, University of Tübingen, Tübingen, Germany.
University of Tübingen · DEHeinrich Heine University Düsseldorf · DENeurocentre Magendie · FRPontificia Universidad Católica Argentina · ARUniversidad de Valladolid · ESUniversité de Bordeaux · FRUniversity College London · GB

Funding

Transmembrane Signaling MechanismsZ01ES101643 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI BIRNBAUMER, LUTZ · 2003 to 2008
$5.1M
Intramural NIH HHS Z01 ES101643
6 · The paper itself

Abstract

BACKGROUND/

aimsFrom invertebrates to mammals, Gαi proteins act together with their common binding partner Gpsm2 to govern cell polarization and planar organization in virtually any polarized cell. Recently, we demonstrated that Gαi3-deficiency in pre-hearing murine cochleae pointed to a role of Gαi3 for asymmetric migration of the kinocilium as well as the orientation and shape of the stereociliary ("hair") bundle, a requirement for the progression of mature hearing. We found that the lack of Gαi3 impairs stereociliary elongation and hair bundle shape in high-frequency cochlear regions, linked to elevated hearing thresholds for high-frequency sound. How these morphological defects translate into hearing phenotypes is not clear.

methodsHere, we studied global and conditional Gnai3 and Gnai2 mouse mutants deficient for either one or both Gαi proteins. Comparative analyses of global versus Foxg1-driven conditional mutants that mainly delete in the inner ear and telencephalon in combination with functional tests were applied to dissect essential and redundant functions of different Gαi isoforms and to assign specific defects to outer or inner hair cells, the auditory nerve, satellite cells or central auditory neurons.

resultsHere we report that lack of Gαi3 but not of the ubiquitously expressed Gαi2 elevates hearing threshold, accompanied by impaired hair bundle elongation and shape in high-frequency cochlear regions. During the crucial reprogramming of the immature inner hair cell (IHC) synapse into a functional sensory synapse of the mature IHC deficiency for Gαi2 or Gαi3 had no impact. In contrast, double-deficiency for Gαi2 and Gαi3 isoforms results in abnormalities along the entire tonotopic axis including profound deafness associated with stereocilia defects. In these mice, postnatal IHC synapse maturation is also impaired. In addition, the analysis of conditional versus global Gαi3-deficient mice revealed that the amplitude of ABR wave IV was disproportionally elevated in comparison to ABR wave I indicating that Gαi3 is selectively involved in generation of neural gain during auditory processing.

conclusionWe propose a so far unrecognized complexity of isoform-specific and overlapping Gαi protein functions particular during final differentiation processes.

Indexed as

AnimalsCarrier ProteinsCell Cycle ProteinsForkhead Transcription FactorsGTP-Binding Protein alpha Subunit, Gi2GTP-Binding Protein alpha Subunits, Gi-GoHair Cells, Auditory, InnerHearingMiceMice, TransgenicNerve Tissue ProteinsCarrier ProteinsCell Cycle ProteinsForkhead Transcription FactorsFoxg1 protein, mouseGnai2 protein, mouseGnai3 protein, mouseGTP-Binding Protein alpha Subunit, Gi2GTP-Binding Protein alpha Subunits, Gi-GoLGN protein, mouseNerve Tissue ProteinsCochlear hair cell maturationDeafness geneGαi3/GNAI3Heterotrimeric G-proteinsNeural gainStereocilia bundle

Identifiers

PMID29940568
PMCPMC11825972
OpenAlexW2810068463

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.