TY  - JOUR
AU  - Hoffmann, Christian
AU  - Rentsch, Jakob
AU  - Tsunoyama, Taka A
AU  - Chhabra, Akshita
AU  - Aguilar Perez, Gerard
AU  - Chowdhury, Rajdeep
AU  - Trnka, Franziska
AU  - Korobeinikov, Aleksandr
AU  - Shaib, Ali H
AU  - Ganzella, Marcelo
AU  - Giannone, Gregory
AU  - Rizzoli, Silvio O
AU  - Kusumi, Akihiro
AU  - Ewers, Helge
AU  - Milovanovic, Dragomir
TI  - Synapsin condensation controls synaptic vesicle sequestering and dynamics.
JO  - Nature Communications
VL  - 14
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2023-01031
SP  - 6730
PY  - 2023
AB  - Neuronal transmission relies on the regulated secretion of neurotransmitters, which are packed in synaptic vesicles (SVs). Hundreds of SVs accumulate at synaptic boutons. Despite being held together, SVs are highly mobile, so that they can be recruited to the plasma membrane for their rapid release during neuronal activity. However, how such confinement of SVs corroborates with their motility remains unclear. To bridge this gap, we employ ultrafast single-molecule tracking (SMT) in the reconstituted system of native SVs and in living neurons. SVs and synapsin 1, the most highly abundant synaptic protein, form condensates with liquid-like properties. In these condensates, synapsin 1 movement is slowed in both at short (i.e., 60-nm) and long (i.e., several hundred-nm) ranges, suggesting that the SV-synapsin 1 interaction raises the overall packing of the condensate. Furthermore, two-color SMT and super-resolution imaging in living axons demonstrate that synapsin 1 drives the accumulation of SVs in boutons. Even the short intrinsically-disordered fragment of synapsin 1 was sufficient to restore the native SV motility pattern in synapsin triple knock-out animals. Thus, synapsin 1 condensation is sufficient to guarantee reliable confinement and motility of SVs, allowing for the formation of mesoscale domains of SVs at synapses in vivo.
KW  - Animals
KW  - Synaptic Vesicles: metabolism
KW  - Synapsins: genetics
KW  - Synapsins: metabolism
KW  - Synapses: metabolism
KW  - Synaptic Transmission: physiology
KW  - Animals, Genetically Modified
KW  - Synapsins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC10593750
C6  - pmid:37872159
DO  - DOI:10.1038/s41467-023-42372-6
UR  - https://pub.dzne.de/record/265756
ER  -