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100 1 _ |a Wang, Huan
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245 _ _ |a Live-cell quantification reveals viscoelastic regulation of synapsin condensates by α-synuclein.
260 _ _ |a Washington, DC [u.a.]
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520 _ _ |a Synapsin and α-synuclein represent a growing list of condensate-forming proteins where the material states of condensates are directly linked to cellular functions (e.g., neurotransmission) and pathology (e.g., neurodegeneration). However, quantifying condensate material properties in living systems has been a substantial challenge. Here, we develop micropipette aspiration and whole-cell patch-clamp (MAPAC), a platform that allows direct material quantification of condensates in live cells. We find 10,000-fold variations in the viscoelasticity of synapsin condensates, regulated by the partitioning of α-synuclein, a marker for synucleinopathies. Through in vitro reconstitutions, we identify multiple molecular factors that distinctly regulate the viscosity, interfacial tension, and maturation of synapsin condensates, confirming the cellular roles of α-synuclein. Overall, our study provides unprecedented quantitative insights into the material properties of neuronal condensates and reveals a crucial role of α-synuclein in regulating condensate viscoelasticity. Furthermore, we envision MAPAC applicable to study a broad range of condensates in vivo.
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650 _ 7 |a alpha-Synuclein
|2 NLM Chemicals
650 _ 7 |a Synapsins
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650 _ 2 |a alpha-Synuclein: metabolism
|2 MeSH
650 _ 2 |a alpha-Synuclein: chemistry
|2 MeSH
650 _ 2 |a Viscosity
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Synapsins: metabolism
|2 MeSH
650 _ 2 |a Synapsins: chemistry
|2 MeSH
650 _ 2 |a Elasticity
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Biomolecular Condensates: metabolism
|2 MeSH
650 _ 2 |a Biomolecular Condensates: chemistry
|2 MeSH
650 _ 2 |a Patch-Clamp Techniques
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700 1 _ |a Hoffmann, Christian
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700 1 _ |a Tromm, Johannes V
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700 1 _ |a Su, Xiao
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700 1 _ |a Elliott, Jordan
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700 1 _ |a Wang, Han
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700 1 _ |a Deng, Mengying
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700 1 _ |a McClenaghan, Conor
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700 1 _ |a Baum, Jean
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700 1 _ |a Pang, Zhiping P
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700 1 _ |a Milovanovic, Dragomir
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700 1 _ |a Shi, Zheng
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773 _ _ |a 10.1126/sciadv.ads7627
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856 4 _ |y OpenAccess
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