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A functional role for GTP-binding proteins in synaptic vesicle cycling
S D Hess1, P A Doroshenko, G J Augustine
1Department of Biological Sciences, University of Southern California.
Science (New York, N.Y.)
|February 19, 1993
Summary
Guanosine-5'-triphosphate (GTP)-binding proteins are crucial for synaptic vesicle distribution in nerve terminals. These proteins regulate vesicle docking and replenishment, essential for neurotransmitter release.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Synaptic transmission relies on the precise regulation of synaptic vesicle distribution.
- Guanosine-triphosphate (GTP)-binding proteins are known regulators of intracellular processes.
Purpose of the Study:
- To investigate the role of GTP-binding proteins in regulating synaptic vesicle distribution.
- To determine if GTP-binding proteins control synaptic vesicle docking and replenishment.
Main Methods:
- Utilized the squid giant synapse model for experimental manipulation.
- Injected nonhydrolyzable GTP and GDP analogs (GTP gamma S, GDP beta S) into presynaptic terminals.
- Measured neurotransmitter release and calcium signals.
- Assessed the number of docked synaptic vesicles.
Main Results:
- GTP gamma S irreversibly inhibited neurotransmitter release.
- Calcium signals and docked vesicle numbers remained unchanged after GTP gamma S injection.
- GDP beta S also inhibited neurotransmitter release, but AIF4- did not.
- GTP gamma S depleted undocked synaptic vesicles, suggesting roles in replenishment.
Conclusions:
- A small molecular weight GTP-binding protein is essential for directing synaptic vesicle docking prior to calcium-dependent release.
- Additional GTP-binding proteins are involved in synaptic vesicle replenishment within nerve terminals.