PSD-95 Involvement in Maturation of Excitatory Synapses

• Published in: Science (American Association for the Advancement of Science) 2000-11, Vol.290 (5495), p.1364-1368
• Main Authors: El-Husseini, Alaa El-Din, Schnell, Eric, Chetkovich, Dane M., Nicoll, Roger A., Bredt, David S.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Biochemistry; Biochemistry and metabolism; Biological and medical sciences; Brain; Cells, Cultured; Central nervous system; Dendrites - ultrastructure; Developmental biology; Developmental Stages; Disks Large Homolog 4 Protein; Excitatory Postsynaptic Potentials; Fundamental and applied biological sciences. Psychology; Hippocampus - cytology; Interneurons; Interneurons - cytology; Interneurons - metabolism; Interneurons - physiology; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Methods; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - physiology; Neurons; Neuroscience; Patch-Clamp Techniques; PDZ protein; Postsynaptic density 95 protein; Presynaptic Terminals - physiology; Protein Structure, Tertiary; Proteins; Pyramidal cells; Pyramidal Cells - cytology; Pyramidal Cells - metabolism; Pyramidal Cells - physiology; Rats; Receptor Aggregation; Receptors; Receptors, AMPA - metabolism; Receptors, Glutamate - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; SAP90-PSD95 Associated Proteins; Synapses; Synapses - metabolism; Synapses - physiology; synaptic clustering; Synaptic Transmission; Synaptic Vesicles - physiology; Transfection; Vertebrates: nervous system and sense organs
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.290.5495.1364

PSD-95 is a neuronal PDZ protein that associates with receptors and cytoskeletal elements at synapses, but whose function is uncertain. We found that overexpression of PSD-95 in hippocampal neurons can drive maturation of glutamatergic synapses. PSD-95 expression enhanced postsynaptic clustering and activity of glutamate receptors. Postsynaptic expression of PSD-95 also enhanced maturation of the presynaptic terminal. These effects required synaptic clustering of PSD-95 but did not rely on its guanylate kinase domain. PSD-95 expression also increased the number and size of dendritic spines. These results demonstrate that PSD-95 can orchestrate synaptic development and are suggestive of roles for PSD-95 in synapse stabilization and plasticity.