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A phospho-switch controls the dynamic association of synapsins with synaptic vesicles
M Hosaka1, R E Hammer, T C Südhof
1Department of Molecular Genetics, Howard Hughes Medical Institute, The University of Texas Southwestern Medical School, Dallas 75235, USA.
Neuron
|November 26, 1999
Summary
Synapsin phosphorylation in the A domain dissociates these synaptic vesicle proteins from vesicles. This phosphorylation-dependent phospholipid-binding mechanism regulates synapsin
Area of Science:
- Molecular and Cellular Neuroscience
- Synaptic Biology
- Protein Phosphorylation
Background:
- Synapsins are key synaptic vesicle proteins regulating neurotransmitter release.
- All synapsins share conserved N-terminal A and central C domains.
- The A domain contains a single, conserved phosphorylation site.
Purpose of the Study:
- To investigate the role of synapsin phosphorylation in the A domain.
- To elucidate the mechanism of synapsin-vesicle association and regulation.
- To explore the function of the A domain in membrane binding.
Main Methods:
- Biochemical assays to study synapsin phosphorylation.
- Analysis of synapsin interaction with synaptic vesicles.
- Phospholipid-binding assays for the synapsin A domain.
Main Results:
- Phosphorylation of the synapsin A domain at its conserved site dissociates synapsins from synaptic vesicles.
- The synapsin A domain directly binds phospholipids.
- Phosphorylation inhibits the phospholipid-binding activity of the A domain.
Conclusions:
- Synapsin association with synaptic vesicles is regulated by phosphorylation-dependent membrane binding.
- This provides a novel mechanism for reversible protein-membrane interactions.
- Dynamic synapsin-vesicle association is linked to synaptic plasticity.