Synucleins Have Multiple Effects on Presynaptic Architecture

Publication date: 3 January 2017
Source:Cell Reports, Volume 18, Issue 1
Author(s): Karina J. Vargas, Nikolas Schrod, Taylor Davis, Ruben Fernandez-Busnadiego, Yumiko V. Taguchi, Ulrike Laugks, Vladan Lucic, Sreeganga S. Chandra
Synucleins (α, β, γ-synuclein) are a family of abundant presynaptic proteins. α-Synuclein is causally linked to the pathogenesis of Parkinson's disease (PD). In an effort to define their physiological and pathological function or functions, we investigated the effects of deleting synucleins and overexpressing α-synuclein PD mutations, in mice, on synapse architecture using electron microscopy (EM) and cryoelectron tomography (cryo-ET). We show that synucleins are regulators of presynapse size and synaptic vesicle (SV) pool organization. Using cryo-ET, we observed that deletion of synucleins increases SV tethering to the active zone but decreases the inter-linking of SVs by short connectors. These ultrastructural changes were correlated with discrete protein phosphorylation changes in αβγ-synuclein−/− neurons. We also determined that α-synuclein PD mutants (PARK1/hA30P and PARK4/hα-syn) primarily affected presynaptic cytomatrix proximal to the active zone, congruent with previous findings that these PD mutations decrease neurotransmission. Collectively, our results suggest that synucleins are important orchestrators of presynaptic terminal topography.

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Teaser

Synucleins (α, β, γ-synuclein) are abundant presynaptic proteins, with α-synuclein linked to the pathogenesis of Parkinson's disease. Vargas et al. investigate the effects of deleting synucleins and overexpressing mutated α-synuclein on synapse architecture using electron microscopy. They find that synucleins regulate presynaptic terminal size and synaptic vesicle distribution.


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