PXD071112

PXD071112 is an original dataset announced via ProteomeXchange.

Title	14-3-3θ Phosphorylation at S232 Reduces its Interactome and Regulates Axonal Trafficking
Description	14-3-3 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.
HostingRepository	PRIDE
AnnounceDate	2025-11-25
AnnouncementXML	Submission_2025-11-24_17:07:50.497.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Talene Yacoubian
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-23 20:34:28	ID requested
⏵ 1	2025-11-24 17:07:51	announced

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;

submitter keyword: Axonal Trafficking, Affinity-purification Mass Spectrometry,14-3-3θ, Parkinson’s disease, Dementia with Lewy Bodies

Talene Alene Yacoubian
contact affiliation	University of Alabama Birmingham Dept of Neurology
contact email	tyacoubian@uabmc.edu
lab head
Talene Yacoubian
contact affiliation	University of Alabama at Birmingham
contact email	tyacoubian@uabmc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD071112
     1. Label: PRIDE project
     2. Name: 14-3-3θ Phosphorylation at S232 Reduces its Interactome and Regulates Axonal Trafficking