Scaffold remodeling in space and time controls synaptic transmission

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Scaffolding proteins in dendritic spines regulate glutamate receptor localization and function, thereby controlling synaptic transmission.
• Understanding the dynamic, spatio-temporal interactions of these scaffolding complexes is crucial for elucidating their function.

Purpose of the Study:

• To investigate the dynamic interaction between GKAP and DLC2, a motor protein, within the postsynaptic density.
• To determine how synaptic activity influences the GKAP-DLC2 interaction and its impact on NMDA receptor function.

Main Methods:

• Combined bioluminescence resonance energy transfer (BRET) imaging with electrophysiological recordings.
• Analyzed protein-protein interactions in real-time within dendritic spines.

Main Results:

• Demonstrated a direct interaction between GKAP and DLC2, modulated by synaptic activity.
• Showed that activity-induced GKAP-DLC2 interaction stabilizes the scaffolding complex in dendritic spines.
• Observed enhancement of NMDA currents due to the GKAP-DLC2 interaction.

Conclusions:

• Synaptic activity dynamically regulates protein-protein interactions within scaffolding complexes.
• The GKAP-DLC2 interaction plays a key role in stabilizing synaptic structure and enhancing NMDA receptor-mediated currents.
• This highlights the bioarchitectural dependence of protein interactions in fine-tuning synaptic transmission.