Condensates of synaptic vesicles and synapsin-1 mediate actin sequestering and polymerization

Area of Science:

• Neuroscience
• Cell Biology
• Biophysics

Background:

• Neuronal communication depends on synaptic vesicle (SV) clusters.
• Synaptic phosphoproteins called synapsins bind actin and are essential for SV clustering via liquid-liquid phase separation.
• The molecular mechanisms linking SVs, synapsins, and actin reorganization during synaptic activity are not fully understood.

Purpose of the Study:

• To investigate the role of SV-synapsin-1 condensates in organizing the presynaptic actin cytoskeleton.
• To elucidate the molecular interactions between SVs, synapsins, and actin.

Main Methods:

• In vitro reconstitution assays
• Expansion microscopy
• Super-resolution imaging
• Cryo-electron tomography

Main Results:

• Synapsin-1 condensation triggers actin polymerization.
• SV-synapsin-actin assemblies organize SV clusters at the mesoscale along axons.
• This organization mirrors native presynaptic structures in lamprey and mammalian synapses.

Conclusions:

• Synapsins are key regulators of the presynaptic actin cytoskeleton.
• SV-synapsin-actin condensates are essential for organizing synaptic vesicle clusters.
• Understanding these interactions is vital for comprehending neural circuit function and behavior.