Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Neurotransmission depends on small synaptic vesicles (SVs) at active zones.
• Synapsin 1 is known to regulate SV clustering.
• Synuclein is an SV-associated protein and synapsin binding partner.

Purpose of the Study:

• To investigate the role of synuclein in SV clustering at vertebrate synapses.
• To determine if synuclein modulates SV docking and distribution at the synapse.

Main Methods:

• Utilized a pan-synuclein antibody to perturb synuclein function in lamprey reticulospinal synapses.
• Assessed the effects of synuclein antibody on SVs, including docked and reserve pools.
• Compared the effects of synuclein antibody with antibodies against SV2 and VAMP/synaptobrevin.

Main Results:

• Pan-synuclein antibody induced significant loss of SVs, depleting docked and reserve pools.
• Synuclein perturbation caused a dose-dependent reduction in synaptic SVs.
• Synuclein disruption led to the dispersion of large SV clusters into smaller ones and individual SVs.

Conclusions:

• Synuclein regulates SV clustering at resting synapses and SV docking at the active zone.
• These findings reveal novel functions of synuclein at the synapse.
• The study provides insights into diseases linked to alpha-synuclein dysfunction, such as Parkinson's disease.