PSD-95 involvement in maturation of excitatory synapses.
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.
El-Husseini
A E
AE
Department of Physiology, University of California, San Francisco 94143, USA.
Schnell
E
E
Chetkovich
D M
DM
Nicoll
R A
RA
Bredt
D S
DS
D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000166:cytology; D007395:Interneurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000502:physiology; D017434:Protein Structure, Tertiary; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011940:Receptor Aggregation; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D000074407:SAP90-PSD95 Associated Proteins; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000502:physiology; D014162:Transfection
D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D000074407:SAP90-PSD95 Associated Proteins; C501449:Dlg4 protein, rat; C409466:NR1 NMDA receptor; C033652:postsynaptic density proteins