Evidence map›Paper›PMID 25675530›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Autism-associated mutation inhibits protein kinase C-mediated neuroligin-4X enhancement of excitatory synapses.

Michael A Bemben, Quynh-Anh Nguyen, Tongguang Wang, Yan Li, Roger A Nicoll, Katherine W Roche

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
5.7field-weighted citation impact, top 4% 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

35 citing papers in PubMed, 60 citations in OpenAlex.

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  7. Regulation of NLGN3 and the Synaptic Rho-GEF Signaling Pathway by CDK5.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
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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 3 institutions in 1 country.

Michael A BembenReceptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892; Department of Biology, The Johns Hopkins University, Baltimore, MD 21218;
Quynh-Anh NguyenDepartments of Cellular and Molecular Pharmacology and Physiology, University of California, San Francisco, CA 94158;
Tongguang WangTranslational Neuroscience Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892; and.
Yan LiProtein/Peptide Sequencing Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Roger A NicollDepartments of Cellular and Molecular Pharmacology and Physiology, University of California, San Francisco, CA 94158; nicoll@cmp.ucsf.edu rochek@ninds.nih.gov.
Katherine W RocheReceptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892; nicoll@cmp.ucsf.edu rochek@ninds.nih.gov.
National Institutes of Health · USUniversity of California, San Francisco · USNational Institute of Neurological Disorders and Stroke · US

Funding

Regulation of Neuroligins and Effects on Synapse Number and FunctionZIANS003140 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI ROCHE, KATHERINE · 2014 to 2025
$20.5M
NEUROTRANSMITTER EFFECTS ON LOCAL NEURONAL CIRCUITSR37MH038256 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NICOLL, ROGER A · 1987 to 2016
$9.0M
NIMH NIH HHS R37 MH038256
6 · The paper itself

Abstract

Autism spectrum disorders (ASDs) comprise a highly heritable, multifarious group of neurodevelopmental disorders, which are characterized by repetitive behaviors and impairments in social interactions. Point mutations have been identified in X-linked Neuroligin (NLGN) 3 and 4X genes in patients with ASDs and all of these reside in their extracellular domains except for a single point mutation in the cytoplasmic domain of NLGN4X in which an arginine is mutated to a cysteine (R704C). Here we show that endogenous NLGN4X is robustly phosphorylated by protein kinase C (PKC) at T707, and R704C completely eliminates T707 phosphorylation. Endogenous NLGN4X is intensely phosphorylated on T707 upon PKC stimulation in human neurons. Furthermore, a phospho-mimetic mutation at T707 has a profound effect on NLGN4X-mediated excitatory potentiation. Our results now establish an important interplay between a genetic mutation, a key posttranslational modification, and robust synaptic changes, which can provide insights into the synaptic dysfunction of ASDs.

Indexed as

Excitatory Postsynaptic PotentialsAmino Acid SequenceAnimalsAutistic DisorderCell Adhesion Molecules, NeuronalHEK293 CellsHumansMolecular Sequence DataMutant ProteinsMutationNeuronsPhosphorylationPhosphothreonineProtein Kinase CRats, Sprague-DawleySynapsesCell Adhesion Molecules, NeuronalMutant ProteinsNLGN4X protein, humanPhosphothreonineProtein Kinase Cautismdevelopmentneuroliginsynaptic adhesion moleculesynaptogenesis

Identifiers

PMID25675530
PMCPMC4345621
OpenAlexW1985475472

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.