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  Vesicle tethering on the surface of phase-separated active zone condensates

Wu, X., Ganzella, M., Zhou, J., Zhu, S., Jahn, R., & Zhang, M. (2020). Vesicle tethering on the surface of phase-separated active zone condensates. Molecular Cell, In Press. doi:10.1016/j.molcel.2020.10.029.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0007-6B20-D Version Permalink: http://hdl.handle.net/21.11116/0000-0007-6B4C-D
Genre: Journal Article

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Wu, X., Author
Ganzella, M.1, Author              
Zhou, J., Author
Zhu, S., Author
Jahn, R.2, Author              
Zhang, M., Author
Affiliations:
1Laboratory of Neurobiology, MPI for Biophysical Chemistry, Max Planck Society, ou_3049887              
2Laboratory of Neurobiology, Max Planck Institute for Biophysical Chemistry, Max Planck Society, ou_3049887              

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Free keywords: liquid-liquid phase separation; biological condensates; membraneless condensates; membrane organelles; presynaptic active zone; postsynaptic density; synapse formation; synaptic transmission
 Abstract: Tethering of synaptic vesicles (SVs) to the active zone determines synaptic strength, although the molecular basis governing SV tethering is elusive. Here, we discover that small unilamellar vesicles (SUVs) and SVs from rat brains coat on the surface of condensed liquid droplets formed by active zone proteins RIM, RIM-BP, and ELKS via phase separation. Remarkably, SUV-coated RIM/RIM-BP condensates are encapsulated by synapsin/SUV condensates, forming two distinct SUV pools reminiscent of the reserve and tethered SV pools that exist in presynaptic boutons. The SUV-coated RIM/RIM-BP condensates can further cluster Ca2+ channels anchored on membranes. Thus, we reconstitute a presynaptic bouton-like structure mimicking the SV-tethered active zone with its one side attached to the presynaptic membrane and the other side connected to the synapsin-clustered SV condensates. The distinct interaction modes between membraneless protein condensates and membrane-based organelles revealed here have general implications in cellular processes, including vesicular formation and trafficking, organelle biogenesis, and autophagy.

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Language(s): eng - English
 Dates: 2020-11-16
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.molcel.2020.10.029
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Title: Molecular Cell
Source Genre: Journal
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