The highly conserved synapsin domain E mediates synapsin dimerization and phospholipid vesicle clustering

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Synapsins are key phosphoproteins regulating synaptic vesicle (SV) dynamics.
• The C-terminal domain E of synapsins is implicated in SV pool formation and exocytosis kinetics.
• The precise molecular mechanisms of domain E's function remain largely unknown.

Purpose of the Study:

• To investigate the role of synapsin domain E in regulating synapsin interactions and SV clustering.
• To elucidate the molecular mechanisms underlying synapsin's effects on SV pools and nerve terminal function.

Main Methods:

• Affinity chromatography and cross-linking assays to study synapsin interactions.
• Atomic force microscopy (AFM) to analyze synapsin binding to liposomes.
• Förster resonance energy transfer (FRET) assays to assess SV-liposome clustering.

Main Results:

• A synthetic peptide from domain E (Pep-E) inhibited synapsin dimerization and binding to SV-mimicking liposomes.
• Pep-E disrupted SV-liposome clustering induced by full-length synapsin I.
• Both domain E and domain C peptides were necessary and sufficient to inhibit dimerization and clustering.

Conclusions:

• Synapsin dimerization and SV clustering are regulated by domain E, providing a molecular basis for its physiological roles.
• These findings offer insights into how synapsins control SV pool size and nerve terminal integrity.