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The core membrane fusion complex governs the probability of synaptic vesicle fusion but not transmitter release kinetics.
The core membrane fusion complex governs the probability of synaptic vesicle fusion but not transmitter release kinetics.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2002 Feb 15; Vol. 22 (4), pp. 1266-72. - Publication Year :
- 2002
-
Abstract
- Synaptic vesicle fusion is driven by the formation of a four-helical bundle composed of soluble N-ethylmaleimide sensitive factor (NSF) attachment protein receptors (SNAREs). Exactly how the structural interactions that lead to the formation of this complex relate to neurotransmitter release is not well understood. To address this question, we used a strategy to "rescue" synaptic transmission after proteolytic cleavage of the synaptosome-associated protein of 25 kDa (SNAP-25) by botulinum neurotoxin E (BoNtE). Transfection of CA3 hippocampal pyramidal cells with BoNtE-resistant SNAP-25 restored synaptic transmission. Additional mutations that alter the interaction between SNAP-25 C-terminal coil and the other SNARE coils dramatically reduce transmitter release probability but leave the kinetics of synaptic responses unaltered. These data indicate that at synapses, SNARE interactions are necessary for fusion but are not the rate-limiting step of neurotransmission.
- Subjects :
- Animals
Biolistics
Botulinum Toxins pharmacology
Electric Stimulation
Excitatory Postsynaptic Potentials drug effects
Excitatory Postsynaptic Potentials physiology
Genes, Reporter
Hippocampus cytology
Hippocampus drug effects
Hippocampus metabolism
In Vitro Techniques
Macromolecular Substances
Membrane Proteins genetics
Membrane Proteins metabolism
Mice
Mutagenesis, Site-Directed
Nerve Tissue Proteins genetics
Nerve Tissue Proteins metabolism
Patch-Clamp Techniques
Pyramidal Cells drug effects
Pyramidal Cells metabolism
SNARE Proteins
Structure-Activity Relationship
Synapses drug effects
Synapses metabolism
Synaptic Transmission drug effects
Synaptosomal-Associated Protein 25
Transfection
Membrane Fusion physiology
Neurotransmitter Agents metabolism
Synaptic Transmission physiology
Synaptic Vesicles metabolism
Vesicular Transport Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 22
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 11850454