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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2006-8-15
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pubmed:abstractText |
Genetic deletion of fragile X mental retardation protein (FMRP) has been shown to enhance mGluR-dependent long-term depression (LTD). Herein, we demonstrate that mGluR-LTD induces a transient, translation-dependent increase in FMRP that is rapidly degraded by the ubiquitin-proteasome pathway. Moreover, proteasome inhibitors abolished mGluR-LTD, and LTD was absent in mice that overexpress human FMRP. Neither translation nor proteasome inhibitors blocked the augmentation of mGluR-LTD in FMRP-deficient mice. In addition, mGluR-LTD is associated with rapid increases in the protein levels of FMRP target mRNAs in wild-type mice. Interestingly, the basal levels of these proteins were elevated and their synthesis was improperly regulated during mGluR-LTD in FMRP-deficient mice. Our findings indicate that hippocampal mGluR-LTD requires the rapid synthesis and degradation of FMRP and that mGluR-LTD triggers the synthesis of FMRP binding mRNAs. These findings indicate that the translation, ubiquitination, and proteolysis of FMRP functions as a dynamic regulatory system for controlling 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/6-methyl-2-(phenylethynyl)pyridine,
http://linkedlifedata.com/resource/pubmed/chemical/Anisomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoates,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Fmr1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Fragile X Mental Retardation Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Glycine,
http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins,
http://linkedlifedata.com/resource/pubmed/chemical/Methoxyhydroxyphenylglycol,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mtap2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Metabotropic Glutamate,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-methyl-4-carboxyphenylglycine,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylleucyl-leucyl-leuci...,
http://linkedlifedata.com/resource/pubmed/chemical/dihydroxyphenylethylene glycol
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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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 |
17
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pubmed:volume |
51
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
441-54
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16908410-Animals,
pubmed-meshheading:16908410-Animals, Newborn,
pubmed-meshheading:16908410-Anisomycin,
pubmed-meshheading:16908410-Benzoates,
pubmed-meshheading:16908410-Blotting, Western,
pubmed-meshheading:16908410-Cysteine Proteinase Inhibitors,
pubmed-meshheading:16908410-Dose-Response Relationship, Drug,
pubmed-meshheading:16908410-Drug Interactions,
pubmed-meshheading:16908410-Excitatory Amino Acid Antagonists,
pubmed-meshheading:16908410-Fluorescent Antibody Technique,
pubmed-meshheading:16908410-Fragile X Mental Retardation Protein,
pubmed-meshheading:16908410-Glycine,
pubmed-meshheading:16908410-Leupeptins,
pubmed-meshheading:16908410-Long-Term Synaptic Depression,
pubmed-meshheading:16908410-Male,
pubmed-meshheading:16908410-Methoxyhydroxyphenylglycol,
pubmed-meshheading:16908410-Mice,
pubmed-meshheading:16908410-Mice, Knockout,
pubmed-meshheading:16908410-Microtubule-Associated Proteins,
pubmed-meshheading:16908410-Models, Biological,
pubmed-meshheading:16908410-Proteasome Endopeptidase Complex,
pubmed-meshheading:16908410-Protein Biosynthesis,
pubmed-meshheading:16908410-Protein Synthesis Inhibitors,
pubmed-meshheading:16908410-Pyridines,
pubmed-meshheading:16908410-RNA, Messenger,
pubmed-meshheading:16908410-Receptors, Metabotropic Glutamate,
pubmed-meshheading:16908410-Signal Transduction
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pubmed:year |
2006
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pubmed:articleTitle |
Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression.
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pubmed:affiliation |
Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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