Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.29.069344v1?rss=1 Authors: Vargas, K. J., Colosi, P. L., Girardi, E., Chandra, S. S. Abstract: -Synuclein plays a central role in Parkinson disease (PD); hence, elucidating its normal physiological function(s) is important. -Synuclein and family members {beta}-, and {gamma}-synuclein, are presynaptically enriched proteins. Synucleins sense and generate membrane curvature, properties consistent with their described roles in synaptic vesicle (SV) cycling. We have previously shown SV endocytosis (SVE) deficits in {beta}{gamma}-synuclein knockout (KO) neurons. Here, we investigate which steps of SVE are regulated by -synuclein. Immuno-electron microscopy (EM) of synaptosomes reveals that -synuclein relocalizes from SVs to the synaptic membrane upon stimulation, allowing -synuclein to function there during or after stimulation. Using membrane recruitment assays, we show that -synuclein is co-localized with clathrin patches. We also observe that recruitment of clathrin and its adaptor, AP180, to synaptic membranes is altered in the absence of synucleins. Visualizing clathrin assembly on membranes in an in vitro reconstitution system reveal that synucleins increase clathrin patch size and curvature, facilitating clathrin coated pit maturation during the early steps of SVE. Copy rights belong to original authors. Visit the link for more info