The postsynaptic density (PSD) is an amorphous structure that is attached to the postsynaptic membrane of glutamatergic synapses. It contains a protein network that targets and anchors postsynaptic components, including glutamate receptors, to the membrane and regulates receptor function. One of the main scaffold proteins, guanylate kinase-associated protein (GKAP, also known as DAP1 and SAPAP), has been shown to bind to the dynein light chain 2 (DLC2), but the importance of this interaction with regards to glutamate receptor trafficking and organisation had not been elucidated. Here, Julie Perroy and co-workers (p. ) describe a function for the GKAP–DLC2 complex in remodelling the postsynaptic complex and modulating the activity of excitatory glutamatergic synapses. Using bioluminescence resonance energy transfer (BRET), they show that neuronal activity enhances the association between GKAP and DLC2. This results in the recruitment of GKAP and an additional scaffold protein, PSD95 (also known as SAP90), to dendritic spines. Electrophysiological measurements reveal that the synaptic clustering of GKAP and PSD95 correlates with enhanced electrical currents, and that this effect is dependent on DLC2. Thus, GKAP, together with DLC2, modulates glutamate receptor activity by altering the postsynaptic protein complex in response to initial neuronal activity.
