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Science 323 (5913): 516-521

Copyright © 2009 by the American Association for the Advancement of Science

Complexin Controls the Force Transfer from SNARE Complexes to Membranes in Fusion

Anton Maximov,1* Jiong Tang,1{dagger} Xiaofei Yang,1,2 Zhiping P. Pang,1,2 Thomas C. Südhof1,2,3,4,5{ddagger}

Abstract: Trans–SNAP receptor (SNARE, where SNAP is defined as soluble NSF attachment protein, and NSF is defined as N-ethylmaleimide–sensitive factor) complexes catalyze synaptic vesicle fusion and bind complexin, but the function of complexin binding to SNARE complexes remains unclear. Here we show that in neuronal synapses, complexin simultaneously suppressed spontaneous fusion and activated fast calcium ion–evoked fusion. The dual function of complexin required SNARE binding and also involved distinct amino-terminal sequences of complexin that localize to the point where trans-SNARE complexes insert into the fusing membranes, suggesting that complexin controls the force that trans-SNARE complexes apply onto the fusing membranes. Consistent with this hypothesis, a mutation in the membrane insertion sequence of the v-SNARE synaptobrevin/vesicle-associated membrane protein (VAMP) phenocopied the complexin loss-of-function state without impairing complexin binding to SNARE complexes. Thus, complexin probably activates and clamps the force transfer from assembled trans-SNARE complexes onto fusing membranes.

1 Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
2 Department of Cellular and Molecular Physiology, Stanford University, 1050 Arastradero Road, Palo Alto, CA 94304–5543, USA.
3 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas TX 75390, USA.
4 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
5 Howard Hughes Medical Institute, Stanford University, Palo Alto, CA 94304–5543, USA.

* Present address: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

{dagger} Present address: Stanford University, Stanford, CA 94305, USA.

{ddagger} To whom correspondence should be addressed. E-mail: tcs1{at}stanford.edu


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