%0 Journal Article
%T Vesicle capture by membrane-bound Munc13-1 requires selfassembly into discrete clusters
%+ Centre de recherche sur l'hétéroepitaxie et ses applications (CRHEA)
%+ Yale School of Medicine [New Haven, Connecticut] (YSM)
%+ Department of Cell Biology [New Haven]
%+ Laboratoire Charles Coulomb (L2C)
%+ Mécanismes Moléculaires Membranaires
%A Li, Feng
%A Sundaram, Venkat, Kalyana
%A Gatta, Alberto, T
%A Coleman, Jeff
%A Ramakrishnan, Sathish
%A Krishnakumar, Shyam, S
%A Pincet, Frederic
%A Rothman, James, E
%Z National Institute of Health (NIH) grant DK027044
%< avec comité de lecture
%@ 0014-5793
%J FEBS Letters
%I Wiley
%V 595
%N 17
%P 2185-2196
%8 2021-07
%D 2021
%R 10.1002/1873-3468.14157
%K Munc13-1
%K cluster
%K SNARE
%K synaptic vesicle
%K neurotransmission
%K membrane fusion
%Z Physics [physics]Journal articles
%X 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.
%G English
%2 https://hal.sorbonne-universite.fr/hal-03297036/document
%2 https://hal.sorbonne-universite.fr/hal-03297036/file/Li%20et%20al.%20-%20Vesicle%20capture%20by%20membrane-bound%20Munc13-1%20require.pdf
%L hal-03297036
%U https://hal.sorbonne-universite.fr/hal-03297036
%~ UNICE
%~ ENS-PARIS
%~ CNRS
%~ L2C
%~ PSL
%~ MIPS
%~ UNIV-MONTPELLIER
%~ UNIV-COTEDAZUR
%~ SORBONNE-UNIVERSITE
%~ SORBONNE-UNIV
%~ LPENS
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%~ UNIVERSITE-PARIS
%~ UP-SCIENCES
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%~ UM-2015-2021