Complexin cooperates with Bruchpilot to tether synaptic vesicles to the active zone cytomatrix

Area of Science:

• Neuroscience
• Molecular Biology
• Synaptic Transmission

Background:

• Synaptic vesicle (SV) release at the presynaptic active zone is vital for nervous system information processing.
• The cytomatrix at the active zone (CAZ) regulates SVs, influencing synaptic efficacy and plasticity.
• SV tethering to CAZ structures involves poorly understood protein interactions.

Purpose of the Study:

• To identify molecules linking Bruchpilot (Brp) C terminus to SVs.
• To investigate the role of Complexin (Cpx) in SV tethering and synaptic function.
• To determine the evolutionary conservation of Cpx's role in synaptic transmission.

Main Methods:

• In vivo screening in *Drosophila melanogaster* to identify SV tethering factors.
• Genetic and functional interaction studies of Brp and Cpx.
• Analysis of SV tethering in *cpx3* knockout mice.

Main Results:

• Complexin (Cpx) was identified as a conserved SNARE regulator linking the Brp C terminus to SVs.
• Brp and Cpx genetically and functionally interact, promoting SV recruitment to the *Drosophila* CAZ.
• Both proteins counteract short-term synaptic depression, indicating a role in maintaining synaptic function.
• Analysis in mice supports a conserved role for Cpx upstream of SNARE complex assembly in SV tethering.

Conclusions:

• Complexin is a key molecular link between the CAZ protein Bruchpilot and synaptic vesicles.
• This interaction is essential for synaptic vesicle recruitment and function, impacting synaptic plasticity.
• The findings highlight an evolutionarily conserved mechanism for synaptic vesicle tethering and neurotransmission.