Evidence map›Paper›PMID 38154503›Full record

ArticleBiological psychiatry2024

Region-Specific Phosphorylation Determines Neuroligin-3 Localization to Excitatory Versus Inhibitory Synapses.

Bekir Altas, Liam P Tuffy, Annarita Patrizi, Kalina Dimova, Tolga Soykan, Cheryl Brandenburg, Andrea J Romanowski, Julia R Whitten, Colin D Robertson, Saovleak N Khim and 15 more

Open access · bronzeAbstract read
In one paragraph

Article in Biological psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

7 citing papers in PubMed, 8 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

25 authors at 5 institutions in 3 countries.

Bekir AltasDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland.
Liam P TuffyDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Annarita PatriziDepartment of Neuroscience Rita Levi Montalcini, University of Turin, Turin, Italy.
Kalina DimovaDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany; Neuroproteomics Group, Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Tolga SoykanDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Cheryl BrandenburgDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland.
Andrea J RomanowskiDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland.
Julia R WhittenDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland.
Colin D RobertsonDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland.
Saovleak N KhimDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland.
Garrett W CrutcherDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland.
Mateusz C AmbrozkiewiczDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Oleksandr YagenskyResearch Group Protein Trafficking in Synaptic Development and Function, Laboratory of Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Dilja Krueger-BurgDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Matthieu HammerDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
He-Hsuan HsiaoBioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Pawel R LaskowskiDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Lydia DyckDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Adam C PucheDepartment of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland.
Marco Sassoè-PognettoDepartment of Neuroscience Rita Levi Montalcini, University of Turin, Turin, Italy.
John J E ChuaResearch Group Protein Trafficking in Synaptic Development and Function, Laboratory of Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Henning UrlaubBioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany; Bioanalytics Group, Institute of Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
Olaf JahnNeuroproteomics Group, Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany; Translational Neuroproteomics Group, Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
Nils BroseDepartment of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Alexandros PoulopoulosDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland; Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany. Electronic address: apoulopoulos@som.umaryland.edu.
Max Planck Institute for Multidisciplinary SciencesUniversity of Maryland, Baltimore · USMax Planck Institute of Experimental Medicine · DEUniversitätsmedizin Göttingen · DEUniversity of Turin · IT

Funding

Training Grant in Cancer BiologyT32CA154274 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI Toni M Antalis, CURT I CIVIN · 2011 to 2026
$6.8M
Multidisciplinary Schizophrenia Research TrainingT32MH067533 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI CARPENTER, WILLIAM T., ELMER, GREGORY I · 2004 to 2025
$4.3M
UMB Postbaccalaureate Research Education ProgramR25GM113262 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI ANTALIS, TONI M, CAREY, GREGORY B · 2016 to 2025
$3.2M
Untangling the biology of brain wiring: high-throughput innovations for molecular screening and functional targeting of circuit development in vivoDP2MH122398 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI POULOPOULOS, ALEXANDROS · 2019 to 2019
$2.3M
NCI NIH HHS T32 CA154274NIGMS NIH HHS R25 GM113262NIMH NIH HHS DP2 MH122398NIMH NIH HHS T32 MH067533
6 · The paper itself

Abstract

backgroundNeuroligin-3 is a postsynaptic adhesion molecule involved in synapse development and function. It is implicated in rare, monogenic forms of autism, and its shedding is critical to the tumor microenvironment of gliomas. While other members of the neuroligin family exhibit synapse-type specificity in localization and function through distinct interactions with postsynaptic scaffold proteins, the specificity of neuroligin-3 synaptic localization remains largely unknown.

methodsWe investigated the synaptic localization of neuroligin-3 across regions in mouse and human brain samples after validating antibody specificity in knockout animals. We raised a phospho-specific neuroligin antibody and used phosphoproteomics, cell-based assays, and in utero CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9) knockout and gene replacement to identify mechanisms that regulate neuroligin-3 localization to distinct synapse types.

resultsNeuroligin-3 exhibits region-dependent synapse specificity, largely localizing to excitatory synapses in cortical regions and inhibitory synapses in subcortical regions of the brain in both mice and humans. We identified specific phosphorylation of cortical neuroligin-3 at a key binding site for recruitment to inhibitory synapses, while subcortical neuroligin-3 remained unphosphorylated. In vitro, phosphomimetic mutation of that site disrupted neuroligin-3 association with the inhibitory postsynaptic scaffolding protein gephyrin. In vivo, phosphomimetic mutants of neuroligin-3 localized to excitatory postsynapses, while phospho-null mutants localized to inhibitory postsynapses.

conclusionsThese data reveal an unexpected region-specific pattern of neuroligin-3 synapse specificity, as well as a phosphorylation-dependent mechanism that regulates its recruitment to either excitatory or inhibitory synapses. These findings add to our understanding of how neuroligin-3 is involved in conditions that may affect the balance of excitation and inhibition.

Indexed as

Cell Adhesion Molecules, NeuronalMembrane ProteinsNerve Tissue ProteinsSynapsesAnimalsBrainFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutPhosphorylationCell Adhesion Molecules, NeuronalMembrane ProteinsNerve Tissue Proteinsneuroligin 3AutismExcitatory synapseInhibitory synapseNeuroliginPhosphorylationScaffolding protein

Identifiers

PMID38154503
PMCPMC11209832
OpenAlexW4390245858

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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.