Evidence map›Paper›PMID 41035411›Full record

ArticleDisease models & mechanisms2025

14-3-3θ phosphorylation at S232 reduces its interactome and regulates axonal trafficking.

F Sanders Pair, Rudradip Pattanayak, James A Mobley, Kyoko Kojima, Mary Gannon, Roschongporn Ekkatine, William J Stone, Kasandra Scholz, Talene A Yacoubian

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Disease models & mechanisms, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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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

1 citing paper in PubMed.

  1. Review
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

9 authors.

F Sanders PairCenter for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.ORCID 0000-0003-0019-0740
Rudradip PattanayakCenter for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
James A MobleyDepartment of Anesthesiology and Perioperative Medicine, Division of Molecular and Translational Biomedicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Kyoko KojimaInstitutional Research Core Program, University of Alabama at Birmingham, Birmingham, AL 35294 , USA.
Mary GannonCenter for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Roschongporn EkkatineCenter for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
William J StoneCenter for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Kasandra ScholzCenter for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Talene A YacoubianCenter for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.ORCID 0000-0003-2227-7310

Funding

14-3-3 phosphorylation in Parkinson's diseaseR01NS112203 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI YACOUBIAN, TALENE ALENE · 2019 to 2023
$2.3M
Effects of 14-3-3θ phosphorylation vesicular transport and alpha-synuclein aggregationRF1NS136240 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI PETIT, CHAD, YACOUBIAN, TALENE ALENE · 2025 to 2025
$1.4M
Role of 14-3-3θ in Environmental Toxicant Exposure and Neuroinflammation in SynucleinopathiesF31ES034985 · NIEHS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI William J Stone · 2023 to 2026
$195k
Causes and Downstream Effects of 14-3-3 Phosphorylation in SynucleinopathiesF31ES034986 · NIEHS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Frank Sanders Pair · 2023 to 2026
$138k
NIEHS NIH HHS F31ES034985NIEHS NIH HHS F31 ES034986NIEHS NIH HHS F31ES034986NINDS NIH HHS R01 NS112203NINDS NIH HHS R01NS112203NINDS NIH HHS R01NS136240NINDS NIH HHS RF1 NS136240Parkinson Association of AlabamaUniversity of Alabama at Birmingham
6 · The paper itself

Abstract

14-3-3 proteins impact protein-protein interactions (PPIs) that regulate neuronal functions. The 14-3-3θ isoform is protective in models of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Human PD and DLB brains show increased 14-3-3θ phosphorylation at S232. To understand the impact of 14-3-3θ phosphorylation on brain PPIs, we performed affinity purification-mass spectrometry using S232 phospho-mutant knock-in mouse models. Proteins binding 14-3-3θ in Cre control cortical lysates were enriched in proteins involved in neuronal morphogenesis and microtubule dynamics. We found a dramatic decrease in proteins binding to 14-3-3θ in S232D mice compared to S232A mice. Axonal trafficking associated with these differentially binding proteins. Live imaging of acidic vesicles in axons revealed reduced net velocity in S232A and S232D neurons compared to that in Cre controls. In S232D neurons, this was due to a dramatic increase in vesicle pausing, while S232A neurons showed reduced segmental velocity, suggesting disrupted dynein motility. We conclude that 14-3-3θ phosphorylation fine tunes axonal transport of acidic vesicles. Disruption of axonal transport with aberrant phosphorylation observed in PD and DLB could contribute to impaired clearance of aggregated proteins in these disorders.

Indexed as

14-3-3 ProteinsAxonal TransportAxonsPhosphoserineSerineAnimalsDyneinsHumansMiceNeuronsPhosphorylationProtein Binding14-3-3 ProteinsDyneinsPhosphoserineSerine14-3-3θAffinity-purification mass spectrometryAxonal traffickingDementia with Lewy bodiesParkinson's disease

Identifiers

PMID41035411
PMCPMC12714136

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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.