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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0072899,
umls-concept:C0185117,
umls-concept:C0205148,
umls-concept:C0243125,
umls-concept:C0699900,
umls-concept:C0851285,
umls-concept:C0900627,
umls-concept:C1333226,
umls-concept:C1519751,
umls-concept:C1705335,
umls-concept:C2911684
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pubmed:issue |
3
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pubmed:dateCreated |
2003-12-3
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Dlgh4 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins,
http://linkedlifedata.com/resource/pubmed/chemical/MDM2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mdm2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-mdm2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, AMPA,
http://linkedlifedata.com/resource/pubmed/chemical/Synapsins,
http://linkedlifedata.com/resource/pubmed/chemical/Tacrolimus,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylleucyl-leucyl-leuci...,
http://linkedlifedata.com/resource/pubmed/chemical/glutamate receptor ionotropic...,
http://linkedlifedata.com/resource/pubmed/chemical/immunomycin,
http://linkedlifedata.com/resource/pubmed/chemical/lactacystin,
http://linkedlifedata.com/resource/pubmed/chemical/postsynaptic density proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0896-6273
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
595-607
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:14642282-Humans,
pubmed-meshheading:14642282-Animals,
pubmed-meshheading:14642282-Kidney,
pubmed-meshheading:14642282-Calcium,
pubmed-meshheading:14642282-Rats,
pubmed-meshheading:14642282-Neurons,
pubmed-meshheading:14642282-Embryo, Mammalian,
pubmed-meshheading:14642282-Mutation,
pubmed-meshheading:14642282-Acetylcysteine,
pubmed-meshheading:14642282-Electric Stimulation,
pubmed-meshheading:14642282-Synapses,
pubmed-meshheading:14642282-Hippocampus,
pubmed-meshheading:14642282-Membrane Proteins,
pubmed-meshheading:14642282-Membrane Potentials,
pubmed-meshheading:14642282-Epitopes,
pubmed-meshheading:14642282-Time Factors,
pubmed-meshheading:14642282-Cells, Cultured,
pubmed-meshheading:14642282-Animals, Newborn,
pubmed-meshheading:14642282-Nerve Tissue Proteins,
pubmed-meshheading:14642282-Patch-Clamp Techniques,
pubmed-meshheading:14642282-Immunoglobulin G,
pubmed-meshheading:14642282-Analysis of Variance,
pubmed-meshheading:14642282-Immunosuppressive Agents,
pubmed-meshheading:14642282-Neural Inhibition,
pubmed-meshheading:14642282-Nuclear Proteins,
pubmed-meshheading:14642282-Immunohistochemistry,
pubmed-meshheading:14642282-Drug Interactions,
pubmed-meshheading:14642282-Rats, Long-Evans,
pubmed-meshheading:14642282-Endocytosis,
pubmed-meshheading:14642282-Leupeptins,
pubmed-meshheading:14642282-Transfection,
pubmed-meshheading:14642282-N-Methylaspartate
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