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Science 335 (6074): 1355-1359

Copyright © 2012 by the American Association for the Advancement of Science

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

Lei Shi,1 Qing-Tao Shen,2 Alexander Kiel,1 Jing Wang,1 Hong-Wei Wang,2 Thomas J. Melia,1 James E. Rothman,1,* Frédéric Pincet1,3,*

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.

1 Department of Cell Biology, School of Medicine, Yale University, New Haven, CT 06520, USA.
2 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
3 Laboratoire de Physique Statistique, UMR CNRS 8550 associée aux Universités Paris 6 et Paris 7, Ecole Normale Supérieure, 24 rue Lhomond, 75005 Paris, France.

* To whom correspondence should be addressed. E-mail: james.rothman{at}yale.edu (J.E.R.); pincet{at}lps.ens.fr (F.P.)

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