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PXD071112-1

PXD071112 is an original dataset announced via ProteomeXchange.

Dataset Summary
Title14-3-3θ Phosphorylation at S232 Reduces its Interactome and Regulates Axonal Trafficking
Description14-3-3 proteins impact protein-protein interactions (PPIs) that regulate neuronal functions. The 14-3-3θ isoform is protective in Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) models. 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 (AP-MS) using S232 phospho-mutant knock-in 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 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 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.
HostingRepositoryPRIDE
AnnounceDate2025-11-25
AnnouncementXMLSubmission_2025-11-24_17:07:50.497.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTalene Yacoubian
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationListNo PTMs are included in the dataset
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-11-23 20:34:28ID requested
12025-11-24 17:07:51announced
Publication List
Pair FS, Pattanayak R, Mobley JA, Kojima K, Gannon M, Ekkatine R, Stone WJ, Scholz K, Yacoubian TA, phosphorylation at S232 reduces its interactome and regulates axonal trafficking. Dis Model Mech, 18(12):(2025) [pubmed]
10.1242/dmm.052405;
Keyword List
submitter keyword: Axonal Trafficking, Affinity-purification Mass Spectrometry,14-3-3θ, Parkinson’s disease, Dementia with Lewy Bodies
Contact List
Talene Alene Yacoubian
contact affiliationUniversity of Alabama Birmingham Dept of Neurology
contact emailtyacoubian@uabmc.edu
lab head
Talene Yacoubian
contact affiliationUniversity of Alabama at Birmingham
contact emailtyacoubian@uabmc.edu
dataset submitter
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