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 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

SUBMITTER: Pair FS 

PROVIDER: S-EPMC12714136 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature