Article

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

Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science (Impact Factor: 33.61). 02/2009; 323(5913):516-21. DOI: 10.1126/science.1166505
Source: PubMed

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.

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    • "Moreover, this ensemble fluorescence study revealed enhanced lipid-mixing upon Ca 2+ triggering with a complexin-1 fragment without the N-terminal and accessory domains. Thus, this lipid-mixing result does not correlate with the observation that the N-terminus of complexin-1 is essential for activation of fast synchronous release (Figure 1EinMaximov et al., 2009). In contrast, our single vesicle–vesicle content-mixing assay correlates well with the physiological data since the N-terminal and accessory domains are required for synchronization of Ca 2+ triggered fusion (Figure 2F,G). "
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