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000265756 1001_ $$0P:(DE-2719)9000582$$aHoffmann, Christian$$b0$$eFirst author$$udzne
000265756 245__ $$aSynapsin condensation controls synaptic vesicle sequestering and dynamics.
000265756 260__ $$a[London]$$bNature Publishing Group UK$$c2023
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000265756 520__ $$aNeuronal 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.
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000265756 650_2 $$2MeSH$$aAnimals
000265756 650_2 $$2MeSH$$aSynaptic Vesicles: metabolism
000265756 650_2 $$2MeSH$$aSynapsins: genetics
000265756 650_2 $$2MeSH$$aSynapsins: metabolism
000265756 650_2 $$2MeSH$$aSynapses: metabolism
000265756 650_2 $$2MeSH$$aSynaptic Transmission: physiology
000265756 650_2 $$2MeSH$$aAnimals, Genetically Modified
000265756 650_7 $$2NLM Chemicals$$aSynapsins
000265756 7001_ $$00000-0002-5728-7255$$aRentsch, Jakob$$b1
000265756 7001_ $$00000-0003-1457-7612$$aTsunoyama, Taka A$$b2
000265756 7001_ $$0P:(DE-2719)9002015$$aChhabra, Akshita$$b3$$udzne
000265756 7001_ $$0P:(DE-2719)9002012$$aAguilar Perez, Gerard$$b4$$udzne
000265756 7001_ $$aChowdhury, Rajdeep$$b5
000265756 7001_ $$0P:(DE-2719)9001331$$aTrnka, Franziska$$b6$$udzne
000265756 7001_ $$0P:(DE-2719)9002676$$aKorobeinikov, Aleksandr$$b7$$udzne
000265756 7001_ $$aShaib, Ali H$$b8
000265756 7001_ $$aGanzella, Marcelo$$b9
000265756 7001_ $$00000-0002-0932-1690$$aGiannone, Gregory$$b10
000265756 7001_ $$00000-0002-1667-7839$$aRizzoli, Silvio O$$b11
000265756 7001_ $$aKusumi, Akihiro$$b12
000265756 7001_ $$00000-0003-3948-4332$$aEwers, Helge$$b13
000265756 7001_ $$0P:(DE-2719)9000670$$aMilovanovic, Dragomir$$b14$$eLast author
000265756 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-023-42372-6$$gVol. 14, no. 1, p. 6730$$n1$$p6730$$tNature Communications$$v14$$x2041-1723$$y2023
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