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A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
GKAP-DLC2 interaction organizes the postsynaptic scaffold complex to enhance synaptic NMDA receptor activity
Enora Moutin1, Fabrice Raynaud, Laurent Fagni
1CNRS, UMR-5203, Institut de Génomique Fonctionnelle, F-34000 Montpellier, France.
Journal of Cell Science
|February 14, 2012
Summary
The guanylate-kinase-associated protein (GKAP)-dynein light chain 2 (DLC2) interaction stabilizes synaptic scaffolding proteins and boosts NMDA receptor activity. This interaction is enhanced by sustained brain activity, revealing a new pathway for regulating synaptic transmission.
Area of Science:
- Neuroscience
- Molecular Biology
- Synaptic Plasticity
Background:
- Scaffolding proteins are crucial for organizing glutamatergic synapses.
- The precise targeting and function of postsynaptic density (PSD) scaffolding proteins remain unclear.
- Guanylate-kinase-associated protein (GKAP) interacts with dynein light chain 2 (DLC2), a protein linked to molecular motors.
Purpose of the Study:
- To investigate the role of the GKAP-DLC2 interaction in the functional organization of glutamatergic synapses.
- To understand how this interaction influences scaffolding protein stability and receptor activity.
Main Methods:
- Bioluminescence Resonance Energy Transfer (BRET) imaging
- Immunostaining techniques
- Electrophysiological recordings
Main Results:
- The GKAP-DLC2 interaction stabilizes scaffolding protein expression at the PSD.
- This interaction enhances synaptic NMDA receptor activity.
- Sustained synaptic activity favors the GKAP-DLC2 functional interaction.
Conclusions:
- The GKAP-DLC2 interaction plays a key role in stabilizing the postsynaptic scaffold.
- This interaction modulates NMDA receptor function in a manner dependent on synaptic activity.
- A novel activity-dependent regulatory pathway for synaptic transmission involving postsynaptic scaffold remodeling has been identified.
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