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Originally published in Science Express on 3 May 2007
Science 25 May 2007:
Vol. 316. no. 5828, pp. 1205 - 1208
DOI: 10.1126/science.1142614
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Reports

How Synaptotagmin Promotes Membrane Fusion

Sascha Martens,1 Michael M. Kozlov,2 Harvey T. McMahon1*

Synaptic vesicles loaded with neurotransmitters are exocytosed in a soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE)–dependent manner after presynaptic depolarization induces calcium ion (Ca2+) influx. The Ca2+ sensor required for fast fusion is synaptotagmin-1. The activation energy of bilayer-bilayer fusion is very high ({approx}40 kBT). We found that, in response to Ca2+ binding, synaptotagmin-1 could promote SNARE-mediated fusion by lowering this activation barrier by inducing high positive curvature in target membranes on C2-domain membrane insertion. Thus, synaptotagmin-1 triggers the fusion of docked vesicles by local Ca2+-dependent buckling of the plasma membrane together with the zippering of SNAREs. This mechanism may be widely used in membrane fusion.

1 Medical Research Council–Laboratory of Molecular Biology, Hills Road, CB2 0QH Cambridge, UK.
2 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.

* To whom correspondence should be addressed. E-mail: hmm{at}mrc-lmb.cam.ac.uk

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