Neuron (Cambridge, Mass.), 2003-10, Vol.40 (3), p.595-607
2003
Details
- Autor(en) / Beteiligte
- Titel
- Ubiquitination Regulates PSD-95 Degradation and AMPA Receptor Surface Expression
- Ist Teil von
- Neuron (Cambridge, Mass.), 2003-10, Vol.40 (3), p.595-607
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2003
- Link zum Volltext
- Quelle
- Electronic Journals Library
- Beschreibungen/Notizen
- PSD-95 is a major scaffolding protein of the postsynaptic density, tethering NMDA- and AMPA-type glutamate receptors to signaling proteins and the neuronal cytoskeleton. Here we show that PSD-95 is regulated by the ubiquitin-proteasome pathway. PSD-95 interacts with and is ubiquitinated by the E3 ligase Mdm2. In response to NMDA receptor activation, PSD-95 is ubiquitinated and rapidly removed from synaptic sites by proteasome-dependent degradation. Mutations that block PSD-95 ubiquitination prevent NMDA-induced AMPA receptor endocytosis. Likewise, proteasome inhibitors prevent NMDA-induced AMPA receptor internalization and synaptically induced long-term depression. This is consistent with the notion that PSD-95 levels are an important determinant of AMPA receptor number at the synapse. These data suggest that ubiquitination of PSD-95 through an Mdm2-mediated pathway is critical in regulating AMPA receptor surface expression during synaptic plasticity.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0896-6273eISSN: 1097-4199DOI: 10.1016/S0896-6273(03)00687-1Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3963808
- Format
- –
- Schlagworte
- Acetylcysteine - analogs & derivatives, Acetylcysteine - pharmacology, Analysis of Variance, Animals, Animals, Newborn, Blotting, Western, Brain, Calcium - metabolism, Cell culture, Cells, Cultured, Colforsin - pharmacology, Cysteine Proteinase Inhibitors - pharmacology, Disks Large Homolog 4 Protein, Drug Interactions, Electric Stimulation, Embryo, Mammalian, Endocytosis, Epitopes - metabolism, Excitatory Amino Acid Agonists - pharmacology, Experiments, Hippocampus - cytology, Hippocampus - drug effects, Hippocampus - physiology, Humans, Immunoglobulin G - metabolism, Immunohistochemistry, Immunosuppressive Agents - pharmacology, In Vitro Techniques, Information storage, Intracellular Signaling Peptides and Proteins, Kidney, Leupeptins - pharmacology, Membrane Potentials - drug effects, Membrane Potentials - physiology, Membrane Proteins, Mutation, N-Methylaspartate - pharmacology, Nerve Tissue Proteins - metabolism, Net losses, Neural Inhibition - drug effects, Neural Inhibition - physiology, Neurons - drug effects, Neurons - metabolism, Nuclear Proteins, Patch-Clamp Techniques, Proteins, Proto-Oncogene Proteins - metabolism, Proto-Oncogene Proteins c-mdm2, Rats, Rats, Long-Evans, Receptors, AMPA - metabolism, Rodents, Statistical analysis, Synapses - drug effects, Synapses - metabolism, Synapsins - metabolism, Tacrolimus - analogs & derivatives, Tacrolimus - pharmacology, Time Factors, Transfection, Ubiquitin - metabolism, Variance analysis