Vesicle Clustering in a Living Synapse Depends on a Synapsin Region that Mediates Phase Separation

Arndt Pechstein, Nikolay Tomilin, Kristin Friedrich, Olga Vorontsova, Elena Sopova, Emma Evergren, Volker Haucke, Lennart Brodin, Oleg Shupliakov

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Abstract

Liquid-liquid phase separation is an increasinglyrecognized mechanism for compartmentalization in cells. Recent in vitro studies suggest that this organizational principle may apply to synaptic vesicle clusters. Here we test this possibility by performing microinjections at the living lamprey giant reticulospinal synapse. Axons are maintained at rest to examine whether reagents introduced into the cytosol enter a putative liquid phase to disrupt critical protein-protein interactions. Compounds that perturb the intrinsically disordered region of synapsin, which is critical for liquid phase organization in vitro, cause dispersion of synaptic vesicles from resting clusters. Reagents that perturb SH3 domain interactions with synapsin are ineffective at rest.Our results indicate that synaptic vesicles at a living central synapse are organized as a distinct liquid phase maintained by interactions via the intrinsically disordered region of synapsin.
Original languageEnglish
Pages (from-to)2594-2602, e1-e3
Number of pages12
JournalCell Reports
Volume30
Issue number8
DOIs
Publication statusPublished - 25 Feb 2020

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    Pechstein, A., Tomilin, N., Friedrich, K., Vorontsova, O., Sopova, E., Evergren, E., Haucke, V., Brodin, L., & Shupliakov, O. (2020). Vesicle Clustering in a Living Synapse Depends on a Synapsin Region that Mediates Phase Separation. Cell Reports, 30(8), 2594-2602, e1-e3. https://doi.org/10.1016/j.celrep.2020.01.092