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

• DOI: 10.1242/jcs.098160
• Publication Date: 2012-02-11T04:27:03Z
• Authors: Enora Moutin; Fabrice Raynaud; Laurent Fagni; Julie Perroy
• Keywords: Neurons; 0301 basic medicine; Tumor Suppressor Proteins; [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology; Nerve Tissue Proteins; Hippocampus; Receptors, N-Methyl-D-Aspartate; SAP90-PSD95 Associated Proteins; Mice; 03 medical and health sciences; Guanylate-kinase-associated protein; Synapses; Animals; Humans; Nuclear Matrix; Dynein light chain; Synaptic transmission; BRET imaging; Scaffolding proteins; Cells, Cultured; Protein Binding

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.