Dataset

DZNE-2025-01443

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Condensates of synaptic vesicles and synapsin-1 mediate actin polymerization

Chhabra, A.DZNE* ; Hoffmann, C.DZNE* ; Aguilar Perez, G.DZNE* ; Korobeinikov, A.DZNE* ; Rentsch, J. ; Hümpfer, N. ; Kokwaro, L.DZNE* ; Gnidovec, L.DZNE* ; Petrovic, A. ; Wallace, J. ; Tromm, J. V.DZNE* ; Roman-Vendrell, C. ; Johnson, E. ; Rankovic, B.DZNE* ; Perego, E. ; Volpi, T. ; Fernandez-Busnadiego, R. ; Köster, S. ; Rizzoli, S. ; Ewers, H. ; Morgan, J. ; Milovanovic, D. (Last author)DZNE*

2025
BioStudies

Abstract: 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.

Note: Deutsche Forschungsgemeinschaft (DFG): MI 2104 SFB 1286/B10 SFB 1286/B02 SFB 1286/B02EC | ERC | HORIZON EUROPE European Research Council (ERC): 101078172HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS): NS078165-12 NS126575-01Deutsche Demenzhilfe: Innovative Minds ProgramGerman Academic Scholarship Foundation: N/A

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Contributing Institute(s):

1. Molecular Neuroscience (AG Milovanovic (Berlin))
2. Molecular Neuroscience (AG Milovanovic (Bonn))

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article Chhabra, A. (First author)DZNE* ; Hoffmann, C. (First author)DZNE* ; Aguilar Perez, G. (First author)DZNE* ; Korobeinikov, A. A.DZNE* ; Rentsch, J. ; Hümpfer, N. ; Kokwaro, L.DZNE* ; Gnidovec, L.DZNE* ; Petrović, A. ; Wallace, J. N. ; Tromm, J. V.DZNE* ; Román-Vendrell, C. ; Johnson, E. C. ; Ranković, B.DZNE* ; Perego, E. ; Volpi, T. ; Fernández-Busnadiego, R. ; Köster, S. ; Rizzoli, S. O. ; Ewers, H. ; Morgan, J. R. ; Milovanovic, D. (Last author)DZNE*
Condensates of synaptic vesicles and synapsin-1 mediate actin sequestering and polymerization.
The EMBO journal 44(18), 5112 - 5148 (2025) [10.1038/s44318-025-00516-y]2025   Files  Fulltext by Pubmed Central BibTeX | EndNote: XML, Text | RIS

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