Journal Article

DZNE-2025-00540

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Live-cell quantification reveals viscoelastic regulation of synapsin condensates by α-synuclein.

Wang, H. ; Hoffmann, C.DZNE* ; Tromm, J. V.DZNE* ; Su, X. ; Elliott, J. ; Wang, H.DZNE* ; Deng, M. ; McClenaghan, C. ; Baum, J. ; Pang, Z. P. ; Milovanovic, D.DZNE* ; Shi, Z.

2025
Assoc. Washington, DC [u.a.]

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Please use a persistent id in citations: doi:10.1126/sciadv.ads7627

Abstract: 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.

Keyword(s): alpha-Synuclein: metabolism (MeSH) ; alpha-Synuclein: chemistry (MeSH) ; Viscosity (MeSH) ; Humans (MeSH) ; Synapsins: metabolism (MeSH) ; Synapsins: chemistry (MeSH) ; Elasticity (MeSH) ; Animals (MeSH) ; Biomolecular Condensates: metabolism (MeSH) ; Biomolecular Condensates: chemistry (MeSH) ; Patch-Clamp Techniques (MeSH) ; alpha-Synuclein ; Synapsins

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Contributing Institute(s):

1. Molecular Neuroscience (AG Milovanovic (Berlin))
2. Molecular Neuroscience (AG Milovanovic (Bonn))

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2025

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