GKAP-DLC2 interaction organizes postsynaptic scaffold complex to enhance synaptic NMDA receptor activity

At glutamatergic brain synapses, scaffolding proteins regulate receptor location and function. The targeting and organization of scaffolding proteins in the postsynaptic density (PSD) is poorly understood. A core protein of the glutamatergic receptor postsynaptic scaffold complex, GKAP, interacts with DLC2, a protein associated with molecular motors. In the present study, we combined BRET imaging, immuno-staining and electrophysiological recording to assess the role of GKAP-DLC2 interaction in the functional organization of the glutamatergic synapse. We found that GKAP-DLC2 interaction in dendritic spine stabilizes scaffolding protein expression at the PSD and enhances synaptic NMDA receptor activity. Moreover, the GKAP-DLC2 functional interaction is favored by sustained synaptic activity. These data provide a novel regulatory pathway of synaptic transmission that depends on activity-induced remodeling of the postsynaptic scaffold protein complex.