TY  - JOUR
AU  - Chhabra, Akshita
AU  - Hoffmann, Christian
AU  - Aguilar Perez, Gerard
AU  - Korobeinikov, Aleksandr A
AU  - Rentsch, Jakob
AU  - Hümpfer, Nadja
AU  - Kokwaro, Linda
AU  - Gnidovec, Luka
AU  - Petrović, Arsen
AU  - Wallace, Jaqulin N
AU  - Tromm, Johannes Vincent
AU  - Román-Vendrell, Cristina
AU  - Johnson, Emma C
AU  - Ranković, Branislava
AU  - Perego, Eleonora
AU  - Volpi, Tommaso
AU  - Fernández-Busnadiego, Rubén
AU  - Köster, Sarah
AU  - Rizzoli, Silvio O
AU  - Ewers, Helge
AU  - Morgan, Jennifer R
AU  - Milovanovic, Dragomir
TI  - Condensates of synaptic vesicles and synapsin-1 mediate actin sequestering and polymerization.
JO  - The EMBO journal
VL  - 44
IS  - 18
SN  - 0261-4189
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2025-01105
SP  - 5112 - 5148
PY  - 2025
AB  - Neuronal communication relies on precisely maintained synaptic vesicle (SV) clusters, which assemble via liquid-liquid phase separation. This process requires synapsins, the major synaptic phosphoproteins, which are known to bind actin. Reorganization of SVs, synapsins, and actin is a hallmark of synaptic activity, but the molecular details of the interactions between these components remain unclear. Here, we combine in vitro reconstitution with expansion microscopy, super-resolution imaging, and cryo-electron tomography to dissect the roles of SV-synapsin-1 condensates in the organization of the presynaptic actin cytoskeleton. Our results indicate that condensation of synapsin-1 initiates actin polymerization. This process enables SV-synapsin-actin assemblies to facilitate the mesoscale organization of SV clusters along axons, which is similar to the native presynaptic organization observed at both lamprey and mammalian synapses. Understanding the relationship between the actin network and synapsin-synaptic vesicle condensates can help elucidate how coordinated neurotransmission along the axon enables circuit function and behavior.
KW  - Synaptic Vesicles: metabolism
KW  - Synaptic Vesicles: ultrastructure
KW  - Synapsins: metabolism
KW  - Animals
KW  - Actins: metabolism
KW  - Polymerization
KW  - Actin Cytoskeleton: metabolism
KW  - Synapses: metabolism
KW  - Actin (Other)
KW  - Liquid-Liquid Phase Separation (Other)
KW  - Presynapses (Other)
KW  - Synapsin (Other)
KW  - Synaptic Vesicles (Other)
KW  - Synapsins (NLM Chemicals)
KW  - Actins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40813925
C2  - pmc:PMC12436662
DO  - DOI:10.1038/s44318-025-00516-y
UR  - https://pub.dzne.de/record/281358
ER  -