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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. (2021). Vesicle tethering on the surface of phase-separated active zone condensates. Molecular Cell, 81(1), 13-24.e7. doi:10.1016/j.molcel.2020.10.029.

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Wu, X., Author
Ganzella, M.1, Author           
Zhou, J., Author
Zhu, S., Author
Jahn, R.1, Author           
Zhang, M., Author
Affiliations:
1Laboratory 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: 2020-11-162021-01-07
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.molcel.2020.10.029
 Degree: -

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Project name : This work was supported by grants from Research Grant Council of Hong Kong (16101419, AoE-M09-12, and C6004-17G), a grant from the Minister of Science and Technology of China (2019YFA0508402 to M.Z.), an ERC Advanced Grant (SVNeuroTrans; to M.G. and R.J.), and a CAPES-Humboldt fellowship (CAPES, 99999.002062/2014-03 to M.G.). M.Z. is a Kerry Holdings Professor of Science and a Senior Fellow of IAS at HKUST. The Biological Cryo-EM Center at HKUST is supported by a donation from the Lo Kwee Seong Foundation.
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Funding organization : -
Project name : SVNeuroTrans
Grant ID : 788259
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)

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Title: Molecular Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 81 (1) Sequence Number: - Start / End Page: 13 - 24.e7 Identifier: ISSN: 1097-2765
CoNE: https://pure.mpg.de/cone/journals/resource/954925610929