Complexin controls the force transfer from SNARE complexes to membranes in fusion
Anton Maximov1, Jiong Tang, Xiaofei Yang
1Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science (New York, N.Y.)
|January 24, 2009
Summary
Complexin controls neuronal membrane fusion by simultaneously suppressing spontaneous events and activating calcium-triggered fusion. This dual function, mediated by SNARE binding and specific sequences, regulates the force of vesicle fusion.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Trans-SNAP receptor (SNARE) complexes are essential for synaptic vesicle fusion.
- Complexin binds to SNARE complexes, but its precise function in fusion regulation is unknown.
Purpose of the Study:
- To elucidate the role of complexin in regulating synaptic vesicle fusion dynamics.
- To investigate how complexin binding influences the force exerted by SNARE complexes.
Main Methods:
- Investigated complexin's dual role in spontaneous and calcium-evoked fusion in neuronal synapses.
- Utilized mutations in complexin and v-SNARE synaptobrevin/vesicle-associated membrane protein (VAMP) to assess functional requirements.
- Examined the localization of complexin's amino-terminal sequences at the membrane insertion site of SNARE complexes.
Main Results:
- Complexin simultaneously suppressed spontaneous fusion and activated fast calcium ion-evoked fusion.
- Complexin's dual function depends on SNARE binding and specific amino-terminal sequences.
- A mutation in the VAMP membrane insertion sequence mimicked complexin loss-of-function without affecting SNARE binding.
Conclusions:
- Complexin acts as a dual regulator of synaptic vesicle fusion, controlling both spontaneous and evoked events.
- Complexin modulates the force transfer from assembled trans-SNARE complexes to the fusing membranes.
- Complexin likely activates and clamps the force generated by SNARE complexes during fusion.
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