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Vesicle capture by membrane-bound Munc13-1 requires selfassembly into discrete clusters

Abstract : Munc13-1 is a large banana-shaped soluble protein that is involved in the regulation of synaptic vesicle docking and fusion. Recent studies suggest that multiple copies of Munc13-1 form nanoassemblies in active zones of neurons. However, it is not known if such clustering of Munc13-1 is correlated with multivalent binding to synaptic vesicles or specific plasma membrane domains at docking sites in the active zone. The functional significance of putative Munc13-1 clustering is also unknown. Here we report that nano-clustering is an inherent property of Munc13-1, and is indeed required for vesicle binding to bilayers containing Munc13-1. Purified Munc13-1 protein reconstituted onto supported lipid bilayers assembled into clusters containing from 2 to ~20 copies as revealed by a combination of quantitative TIRF microscopy and step-wise photobleaching. Surprisingly, only clusters containing a minimum of 6 copies of Munc13-1 were capable of efficiently capturing and retaining small unilamellar vesicles. The C-terminal C 2 C domain of Munc13-1 is not required for Munc13-1 clustering, but is required for efficient vesicle capture. This capture is largely due to a combination of electrostatic and hydrophobic interactions between the C 2 C domain and the vesicle membrane.
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Submitted on : Friday, July 23, 2021 - 10:03:23 AM
Last modification on : Tuesday, December 7, 2021 - 4:10:07 PM
Long-term archiving on: : Sunday, October 24, 2021 - 6:12:52 PM

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Feng Li, Venkat Sundaram, Alberto Gatta, Jeff Coleman, Sathish Ramakrishnan, et al.. Vesicle capture by membrane-bound Munc13-1 requires selfassembly into discrete clusters. FEBS Letters, Wiley, 2021, ⟨10.1002/1873-3468.14157⟩. ⟨hal-03297036⟩

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