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Data · dataset · 2021

Proteomic and quantitative data of dopaminergic neuron vesicles potentiated by beta-synuclein after MPTP-induced toxicity

Listed in Teesside University Research Data Repository

Previous studies have demonstrated the importance of alpha-synuclein as a modulator of various mechanisms implicated in chemical neurotransmission but information about other two synuclein family members’ involvement in molecular processes taking place in presynaptic terminals is limited.

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Here we demonstrated that dopamine uptake by synaptic vesicles isolated from the striatum of mice lacking beta-synuclein was significantly reduced.

Reciprocally, reintroduction, either in vivo or in vitro, of beta-synuclein but not alpha- or gamma-synuclein improved uptake by vesicles isolated from the striatum of triple-alpha/beta/gamma-synuclein deficient mice. Proteomic analysis of synuclein-free and beta-synuclein-only-containing synaptic vesicles suggested that mechanistically, beta-synuclein potentiates vesicular monoamine transporter 2 (VMAT2)-dependent dopamine uptake by assembling specific multiprotein complexes comprised of resident vesicular proteins and transiently associated predominantly cytosolic proteins.

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The increased availability of such complexes on the surface of striatal synaptic vesicles lacking other synucleins should also promote sequestration of 1-methyl-4-phenylpyridinium (MPP+), a toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which explains the resistance of dopaminergic neurons of substantia nigra lacking alpha-synuclein and/or gamma-synuclein to this neurotoxin. The present data demonstrate the rational distribution of the most significantly altered proteins between WT, TKO, and alpha/gamma-synuclein KO striatal vesicle proteomes.

Data cover essential information regarding proteomic assay.

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