Dataset Information

14-3-3θ Phosphorylation at S232 Reduces its Interactome and Regulates Axonal Trafficking

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Parkinson's Disease

SUBMITTER: Talene Yacoubian

LAB HEAD: Talene Alene Yacoubian

PROVIDER: PXD071112 | Pride | 2025-11-25

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	14-3-3APMS_Yacoubian_MF_combined.sf3	Other
	CodeMassSpecPaper.py	Other
	Mouse_IDs.xlsx	Xlsx
	Supp_File_1_General_14-3-3_theta_Interactors.xlsx	Xlsx
	Supp_File_2_A_vs_D_Mass_spec_data.xlsx	Xlsx

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Publications

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

Pair F Sanders FS Pattanayak Rudradip R Mobley James A JA Kojima Kyoko K Gannon Mary M Ekkatine Roschongporn R Stone William J WJ Scholz Kasandra K Yacoubian Talene A TA

Disease models & mechanisms 20251205 12

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 ...[more]

PMID: 41035411

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