Evidence map›Paper›PMID 42244611›Full record

ArticlebioRxiv : the preprint server for biology2026

An atomic interaction conserved for over 600 million years gates inhibitory neurotransmission.

Cecilia M Borghese, Netrang G Desai, Pranavi Garlapati, Syedah K Shah, Jason D Galpin, Luthary Segura, Nandan Haloi, Harold H Zakon, Rebecca J Howard, Erik Lindahl and 2 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Cecilia M BorgheseDepartment of Neuroscience, The University of Texas at Austin, Austin, TX, USA.ORCID 0000-0002-1028-8277
Netrang G DesaiDepartment of Neuroscience, The University of Texas at Austin, Austin, TX, USA.ORCID 0009-0001-5807-1413
Pranavi GarlapatiDepartment of Neuroscience, The University of Texas at Austin, Austin, TX, USA.ORCID 0000-0002-0338-9053
Syedah K ShahDepartment of Neuroscience, The University of Texas at Austin, Austin, TX, USA.
Jason D GalpinDepartment of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, USA.ORCID 0000-0003-1923-5312
Luthary SeguraDepartment of Neuroscience, The University of Texas at Austin, Austin, TX, USA.ORCID 0000-0003-3150-3754
Nandan HaloiDepartment of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.ORCID 0000-0003-3542-333X
Harold H ZakonDepartment of Neuroscience, The University of Texas at Austin, Austin, TX, USA.ORCID 0000-0002-3700-4668
Rebecca J HowardDepartment of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.ORCID 0000-0003-2049-3378
Erik LindahlDepartment of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.ORCID 0000-0002-2734-2794
Christopher A AhernDepartment of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, USA.ORCID 0000-0002-7975-2744
Marcel P Goldschen-OhmDepartment of Neuroscience, The University of Texas at Austin, Austin, TX, USA.ORCID 0000-0003-1466-9808

Funding

Chemical biology of voltage-gated cation channelsR35GM148239 · NIGMS · UNIVERSITY OF IOWA · PI Christopher A Ahern · 2023 to 2026
$2.5M
Mechanisms of stepwise activation and drug-modulation in ligand-gated ion channels.R01GM148591 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI GOLDSCHEN-OHM, MARCEL PAZ · 2022 to 2025
$1.3M
NIGMS NIH HHS R01 GM148591NIGMS NIH HHS R35 GM148239
6 · The paper itself

Abstract

Pentameric ligand-gated ion channels (pLGICs) mediate fast inhibitory neurotransmission critical for neuronal network stability. A tyrosine residue in the M2-M3 linker of inhibitory pLGICs, conserved for over 600 million years, is positioned where it could hydrogen bond (H-bond) to the backbone of the neighboring Cys-loop. Given the pathogenic effects of variants of this tyrosine, we hypothesized that this H-bond stabilizes extracellular-to-transmembrane domain coupling essential for channel gating. To test this hypothesis, we used site-directed mutagenesis, noncanonical amino acid incorporation, and electrophysiological recordings in

Indexed as

GABA receptorglycine receptorhydrogen bondion channel gatingLigand-gated ion channels

Identifiers

PMID42244611
PMCPMC13232294

What OpenQuestion holds

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Registered trials

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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.