000154773 001__ 154773 000154773 005__ 20230915092313.0 000154773 0247_ $$2doi$$a10.1016/j.jmb.2021.166961 000154773 0247_ $$2pmid$$apmid:33774037 000154773 0247_ $$2ISSN$$a0022-2836 000154773 0247_ $$2ISSN$$a1089-8638 000154773 0247_ $$2altmetric$$aaltmetric:103000811 000154773 037__ $$aDZNE-2021-00363 000154773 041__ $$aEnglish 000154773 082__ $$a610 000154773 1001_ $$0P:(DE-2719)9000582$$aHoffmann, Christian$$b0$$eFirst author 000154773 245__ $$aSynapsin Condensates Recruit alpha-Synuclein. 000154773 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2021 000154773 3367_ $$2DRIVER$$aarticle 000154773 3367_ $$2DataCite$$aOutput Types/Journal article 000154773 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1683797294_30877 000154773 3367_ $$2BibTeX$$aARTICLE 000154773 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000154773 3367_ $$00$$2EndNote$$aJournal Article 000154773 520__ $$aNeurotransmission relies on the tight spatial and temporal regulation of the synaptic vesicle (SV) cycle. Nerve terminals contain hundreds of SVs that form tight clusters. These clusters represent a distinct liquid phase in which one component of the phase are SVs and the other synapsin 1, a highly abundant synaptic protein. Another major family of disordered proteins at the presynapse includes synucleins, most notably α-synuclein. The precise physiological role of α-synuclein in synaptic physiology remains elusive, albeit its role has been implicated in nearly all steps of the SV cycle. To determine the effect of α-synuclein on the synapsin phase, we employ the reconstitution approach using natively purified SVs from rat brains and the heterologous cell system to generate synapsin condensates. We demonstrate that synapsin condensates recruit α-synuclein, and while enriched into these synapsin condensates, α-synuclein still maintains its high mobility. The presence of SVs enhances the rate of synapsin/α-synuclein condensation, suggesting that SVs act as catalyzers for the formation of synapsin condensates. Notably, at physiological salt and protein concentrations, α-synuclein alone is not able to cluster isolated SVs. Excess of α-synuclein disrupts the kinetics of synapsin/SV condensate formation, indicating that the molar ratio between synapsin and α-synuclein is important in assembling the functional condensates of SVs. Understanding the molecular mechanism of α-synuclein interactions at the nerve terminals is crucial for clarifying the pathogenesis of synucleinopathies, where α-synuclein, synaptic proteins and lipid organelles all accumulate as insoluble intracellular inclusions. 000154773 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x0 000154773 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x1 000154773 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000154773 650_7 $$2Other$$aliquid-liquid phase separation 000154773 650_7 $$2Other$$asynapsin 1 000154773 650_7 $$2Other$$asynaptic vesicles 000154773 650_7 $$2Other$$asynucleinopathies 000154773 650_7 $$2Other$$aα-synuclein 000154773 650_2 $$2MeSH$$aAnimals 000154773 650_2 $$2MeSH$$aBrain: cytology 000154773 650_2 $$2MeSH$$aBrain: metabolism 000154773 650_2 $$2MeSH$$aHEK293 Cells 000154773 650_2 $$2MeSH$$aHumans 000154773 650_2 $$2MeSH$$aLuminescent Proteins: genetics 000154773 650_2 $$2MeSH$$aLuminescent Proteins: metabolism 000154773 650_2 $$2MeSH$$aMacromolecular Substances: chemistry 000154773 650_2 $$2MeSH$$aMacromolecular Substances: metabolism 000154773 650_2 $$2MeSH$$aMicroscopy, Confocal 000154773 650_2 $$2MeSH$$aMicroscopy, Fluorescence 000154773 650_2 $$2MeSH$$aRats 000154773 650_2 $$2MeSH$$aSynapsins: chemistry 000154773 650_2 $$2MeSH$$aSynapsins: metabolism 000154773 650_2 $$2MeSH$$aSynaptic Transmission 000154773 650_2 $$2MeSH$$aSynaptic Vesicles: metabolism 000154773 650_2 $$2MeSH$$aalpha-Synuclein: chemistry 000154773 650_2 $$2MeSH$$aalpha-Synuclein: metabolism 000154773 7001_ $$0P:(DE-2719)9000736$$aSansevrino, Roberto$$b1$$eFirst author 000154773 7001_ $$0P:(DE-2719)9001233$$aMorabito, Giuseppe$$b2 000154773 7001_ $$0P:(DE-2719)9001041$$aLogan, Chinyere$$b3 000154773 7001_ $$0P:(DE-HGF)0$$aVabulas, R Martin$$b4 000154773 7001_ $$0P:(DE-2719)2772760$$aUlusoy, Ayse$$b5 000154773 7001_ $$0P:(DE-HGF)0$$aGanzella, 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