PSD-95 involvement in maturation of excitatory synapses

PSD-95 is a neuronal PDZ protein that associates with receptors and cytoske letal elements at synapses, but whose function is uncertain. We found that overexpression of PSD-95 in hippocampal neurons can drive maturation of glu tamatergic synapses. PSD-95 expression enhanced postsynaptic clustering and activity of glutamate receptors. Postsynaptic expression of PSD-95 also en hanced maturation of the presynaptic terminal. These effects required synap tic clustering of PSD-95 but did not rely on its guanylate kinase domain. P SD-95 expression also increased the number and size of dendritic spines. Th ese results demonstrate that PSD-95 can orchestrate synaptic development an d are suggestive of roles for PSD-95 in synapse stabilization and plasticit y.