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Condensates of synaptic vesicles and synapsin are molecular beacons for actin sequestering and polymerization

Title: Condensates of synaptic vesicles and synapsin are molecular beacons for actin sequestering and polymerization
Authors: Chhabra, Akshita; Hoffmann, Christian; Pérez, Gerard Aguilar; Korobeinikov, Aleksandr A; Rentsch, Jakob; Hümpfer, Nadja; Kokwaro, Linda; Gnidovec, Luka; Petrovic, Arsen; Wallace, Jaqulin N; Tromm, Johannes Vincent; Román-Vendrell, Cristina; Johnson, Emma C; Ranković, Branislava; Perego, Eleonora; Volpi, Tommaso; Fernández-Busnadiego, Rubén; Köster, Sarah; Rizzoli, Silvio O; Ewers, Helge; Morgan, Jennifer R; Milovanovic, Dragomir
Contributors: Chhabra, Akshita; Hoffmann, Christian; Pérez, Gerard Aguilar; Korobeinikov, Aleksandr A; Rentsch, Jakob; Hümpfer, Nadja; Kokwaro, Linda; Gnidovec, Luka; Petrovic, Arsen; Wallace, Jaqulin N; Tromm, Johannes Vincent; Román-Vendrell, Cristina; Johnson, Emma C; Ranković, Branislava; Perego, Eleonora; Volpi, Tommaso; Fernández-Busnadiego, Rubén; Köster, Sarah; Rizzoli, Silvio O; Ewers, Helge; Morgan, Jennifer R; Milovanovic, Dragomir
Publication Year: 2025
Collection: Georg-August-Universität Göttingen: GoeScholar
Subject Terms: neuro biophysics; cytoskeleton
Description: Neuronal communication relies on precisely maintained synaptic vesicle (SV) clusters, which assemble via liquid-liquid phase separation (LLPS). This process requires synapsins, the major synaptic phosphoproteins, which are known to bind actin. The reorganization of SVs, synapsins and actin is a hallmark of synaptic activity, but their interplay is still unclear. Here, we combined the reconstitution approaches, expansion microscopy, super-resolution imaging and cryo-electron tomography to dissect the roles of synapsin-SV condensates in the organization of the presynaptic actin cytoskeleton. Our data indicate that LLPS of synapsin initiates actin polymerization, allowing for SV:synapsin:actin assemblies to facilitate the mesoscale organization of SV clusters along axons mimicking the native presynaptic organization in both lamprey and mammalian synapses. Understanding the relationship between the actin network and synapsin-SVs condensates is an essential building block on a roadmap to unravel how coordinated neurotransmission along the axon enables circuit function and behavior.
Document Type: report
Language: English
DOI: 10.1101/2024.07.19.604346
Availability: https://resolver.sub.uni-goettingen.de/purl?gro-2/149288; https://doi.org/10.1101/2024.07.19.604346; https://publications.goettingen-research-online.de/handle/2/145063
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.19DCE99B
Database: BASE