Concurrent binding of complexin and synaptotagmin to liposome-embedded SNARE complexes
Michael C Chicka1, Edwin R Chapman
1Department of Physiology and Programs in Cellular and Molecular Biology, University of Wisconsin, 1300 University Avenue, SMI 129, Madison, Wisconsin 53706, USA.
Biochemistry
|January 9, 2009
Summary
Complexin and synaptotagmin both inhibit SNARE-mediated fusion. Calcium-bound synaptotagmin accelerates fusion, while complexin inhibits it, revealing distinct roles in synaptic vesicle exocytosis.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Synaptotagmin and complexin are key regulators of SNARE-mediated synaptic vesicle exocytosis.
- Previous models proposed complexin clamps fusion, with Ca(2+)-synaptotagmin relieving this clamp.
Purpose of the Study:
- To investigate the distinct roles of synaptotagmin and complexin in regulating SNARE-mediated membrane fusion.
- To clarify the mechanism by which Ca(2+) triggers fusion in the presence of these proteins.
Main Methods:
- Utilized a reconstituted system to study protein-SNARE interactions and membrane fusion.
- Analyzed the binding and inhibitory activities of synaptotagmin and complexin on SNARE complexes.
Main Results:
- Both apo-synaptotagmin and complexin inhibit SNARE-mediated fusion.
- Apo-synaptotagmin's inhibitory activity occludes complexin's until Ca(2+) arrival.
- Ca(2+)-synaptotagmin accelerates fusion, whereas high complexin concentrations inhibit it.
Conclusions:
- Synaptotagmin and complexin exhibit different inhibitory patterns on SNARE fusion.
- SNARE complexes may assemble into distinct states during the fusion pathway.
- Complexin does not function as a Ca(2+)-synaptotagmin-relieved clamp in vesicle-vesicle fusion.
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