UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Li, Feng; Sundaram, Ramalingam Venkat Kalyana; Gatta, Alberto T; Coleman, Jeff; Ramakrishnan, Sathish; Krishnakumar, Shyam S; Pincet, Frederic; (2021) Vesicle capture by membrane-bound Munc13-1 requires self-assembly into discrete clusters. FEBS Letters , 595 (17) pp. 2185-2196. 10.1002/1873-3468.14157.

[thumbnail of Rothman_Vesicle capture by discrete self-assembled clusters of membrane- bound Munc13-1.pdf] Text
Rothman_Vesicle capture by discrete self-assembled clusters of membrane- bound Munc13-1.pdf - Accepted Version
Access restricted to UCL open access staff until 25 July 2022.

Download (928kB)

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 nano-assemblies in active zones of neurons. However, it is not known whether 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 C2C 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 C2C domain and the vesicle membrane.

Type: Article
Title: Vesicle capture by membrane-bound Munc13-1 requires self-assembly into discrete clusters
Location: England
DOI: 10.1002/1873-3468.14157
Publisher version: https://doi.org/10.1002/1873-3468.14157
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: cluster; membrane fusion; Munc13-1; neurotransmission SNARE; synaptic vesicle
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10150755
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item