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Structural transitions in the synaptic SNARE complex during Ca2+-triggered exocytosis.
1Department of Physiology, University of Wisconsin Medical School, Madison, WI 53706, USA.
The Journal of Cell Biology
|January 19, 2006
Summary
This study reveals the synaptic SNARE complex undergoes distinct structural transitions during exocytosis, challenging the idea of simple zipping. Mutations impact fusion pore opening and dilation, suggesting complex conformational changes drive neurotransmitter release.
Area of Science:
- Biochemistry
- Cell Biology
- Neuroscience
Background:
- The synaptic SNARE complex is crucial for Ca(2+)-triggered release of neurotransmitters and hormones.
- Mechanisms of SNARE complex assembly and structural transitions during exocytosis remain unclear.
Purpose of the Study:
- To investigate SNARE complex assembly and structural dynamics during exocytosis.
- To elucidate the role of specific mutations in the SNARE complex hydrophobic core on membrane fusion.
Main Methods:
- Site-directed mutagenesis of the SNARE complex hydrophobic core.
- Amperometry to measure fusion pore opening and dilation dynamics.
Main Results:
- Mutations throughout the SNARE complex differentially affected two rate processes preceding fusion pore opening.
- Distinct, fully assembled SNARE complex conformations appear to drive initial fusion pore opening.
- Mutations in the membrane-distal half stabilized open fusion pores, suggesting a role in dilation.
- A partially disassembled complex likely drives fusion pore dilation.
Conclusions:
- SNARE complex function in exocytosis involves distinct conformational states, not simple vectorial zipping.
- Structural transitions within the SNARE complex regulate both fusion pore initiation and dilation.