Synapsin condensation controls synaptic vesicle sequestering and dynamics

Synapsin condensation controls synaptic vesicle sequestering and dynamics

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...

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Published in:Nature communications Vol. 14; no. 1; p. 6730
Main Authors: Hoffmann, Christian, Rentsch, Jakob, Tsunoyama, Taka A., Chhabra, Akshita, Aguilar Perez, Gerard, Chowdhury, Rajdeep, Trnka, Franziska, Korobeinikov, Aleksandr A., Shaib, Ali H., Ganzella, Marcelo, Giannone, Gregory, Rizzoli, Silvio O., Kusumi, Akihiro, Ewers, Helge, Milovanovic, Dragomir
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 23-10-2023
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Subjects:
14/19
14/34
14/35
14/63
140/125
631/378/340
631/45/56
631/80/313
82/1
82/16
82/80
82/83
Axons
Condensates
Condensation
Confinement
Humanities and Social Sciences
Image resolution
Motility
multidisciplinary
Neuroimaging
Neurotransmitter release
Neurotransmitters
Presynapse
Science
Science (multidisciplinary)
Sequestering
Synapses
Synapsin
Synaptic vesicles
Vesicles
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Summary: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. Brain functioning critically relies on coordinated neurotransmitter release by synaptic vesicles (SVs) at synapses. This study shows that synapsin/SVs condensation is sufficient to guarantee reliable confinement and motility of SVs at synapses in vivo.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-42372-6