Lipidic antagonists to SNARE-mediated fusion
Thomas J Melia1, Daoqi You, David C Tareste
1Department of Physiology and Cellular Biophysics, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA. tm2176@columbia.edu
The Journal of Biological Chemistry
|August 5, 2006
Summary
Acyl-CoAs inhibit membrane fusion by blocking SNARE assembly. Removing these lipids triggers a fusion burst, revealing semi-assembled SNARE complexes that are resistant to cleavage, suggesting dynamic SNAREpin interactions.
Area of Science:
- Biochemistry
- Cell Biology
- Membrane Biophysics
Background:
- SNARE proteins are essential for mediating membrane fusion events.
- Lipid bilayer deformation is a critical step in the fusion process.
- Acyl-CoAs act as antagonists, inhibiting membrane fusion.
Purpose of the Study:
- To investigate the role of lipidic antagonists in SNARE assembly.
- To characterize SNARE complex formation up to stalk formation.
- To understand the dynamics of SNARE complex assembly during membrane fusion.
Main Methods:
- Utilized inverted cone-shaped lipids (acyl-CoAs) as fusion antagonists.
- Assessed SNARE assembly extent and range by monitoring membrane fusion.
- Investigated the effect of VAMP2 soluble domain on SNARE complex recovery.
Main Results:
- Acyl-CoAs inhibit fusion in an acyl-chain length-dependent manner.
- Removal of acyl-CoA leads to a burst of membrane fusion, indicating accumulated semi-assembled SNARE complexes.
- These complexes resist cleavage by botulinum toxin B, suggesting advanced assembly.
- VAMP2 soluble domain inhibits recovery from acyl-CoA inhibition.
Conclusions:
- SNARE complex formation requires progression through to membrane fusion for tight assembly.
- Physiologically docked exocytic vesicles may be anchored by dynamic SNAREpins.
- Lipidic antagonists provide insights into the stages of SNARE-mediated fusion.
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