SNARE Proteins: One to Fuse and Three to Keep the Nascent Fusion Pore Open

Overview

Journal Science

Specialty Science

Date 2012 Mar 17

PMID 22422984

Citations 163

Authors

Lei Shi

Qing-Tao Shen

Alexander Kiel

Jing Wang

Hong-Wei Wang

Thomas J Melia

James E Rothman

Frederic Pincet

Affiliations

Soon will be listed here.

Abstract

Neurotransmitters are released through nascent fusion pores, which ordinarily dilate after bilayer fusion, preventing consistent biochemical studies. We used lipid bilayer nanodiscs as fusion partners; their rigid protein framework prevents dilation and reveals properties of the fusion pore induced by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor). We found that although only one SNARE per nanodisc is required for maximum rates of bilayer fusion, efficient release of content on the physiologically relevant time scale of synaptic transmission apparently requires three or more SNARE complexes (SNAREpins) and the native transmembrane domain of vesicle-associated membrane protein 2 (VAMP2). We suggest that several SNAREpins simultaneously zippering their SNARE transmembrane helices within the freshly fused bilayers provide a radial force that prevents the nascent pore from resealing during synchronous neurotransmitter release.

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