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rdf:type |
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lifeskim:mentions |
umls-concept:C0007765,
umls-concept:C0011570,
umls-concept:C0015252,
umls-concept:C0067966,
umls-concept:C0072899,
umls-concept:C0243126,
umls-concept:C0443252,
umls-concept:C0728940,
umls-concept:C1417857,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636
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pubmed:issue |
52
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pubmed:dateCreated |
2004-12-29
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pubmed:abstractText |
Cerebellar long-term depression (LTD) is a persistent attenuation of synaptic transmission at the parallel fiber-Purkinje cell synapse mediated by the removal of GluR2 subunit-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The removal of AMPA receptors requires protein kinase C phosphorylation of the GluR2 subunit within its carboxyl-terminal PSD-95/Discs Large/Zona Occludens-1 (PDZ) ligand and binding of the PDZ domain-containing protein, PICK1. The sequence of the GluR2 subunit is similar to that of the GluR3 and GluR4c subunits, which also contain PDZ ligands and protein kinase C consensus sites. Although GluR3 and GluR4c are also expressed in Purkinje cells, we have previously shown that cerebellar LTD is absent in GluR2(-/-) mice, suggesting that these subunits are unable to substitute functionally for GluR2. Here, we examine the apparent difference in the regulation of these AMPA receptor subunits by attempting to rescue LTD in GluR2(-/-) Purkinje cells with WT and mutant GluR2 and GluR3 subunits. Our results show that the selective interaction of the GluR2 subunit with the N-ethylmaleimide-sensitive factor protein is required for synaptic, but not extrasynaptic, incorporation of AMPA receptors as well as for their competence to undergo LTD. In addition, perfusion of a synthetic peptide that acutely disrupts the interaction of GluR2 with N-ethylmaleimide-sensitive factor selectively depletes GluR2-containing receptors from synapses and occludes LTD. These findings demonstrate that interaction of AMPA receptors with N-ethylmaleimide-sensitive factor plays a critical role in incorporation of AMPA receptors into synapses and for their subsequent removal during cerebellar LTD.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-10399941,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-10571232,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-10595516,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-10774731,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-10856222,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-11144359,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-11707583,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-11931741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-12052905,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-12392933,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-12441055,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-12805550,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-1370372,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-15037235,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-15541307,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-1653450,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-186587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-2238044,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-8938126,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-9697854,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15608060-9728920
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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/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Ethylmaleimide,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/N-Ethylmaleimide-Sensitive Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nsf protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Prkcabp protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, AMPA,
http://linkedlifedata.com/resource/pubmed/chemical/Vesicular Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/glutamate receptor ionotropic...
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
18212-6
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:15608060-Amino Acid Sequence,
pubmed-meshheading:15608060-Animals,
pubmed-meshheading:15608060-Carrier Proteins,
pubmed-meshheading:15608060-Cerebellum,
pubmed-meshheading:15608060-DNA, Complementary,
pubmed-meshheading:15608060-Depression,
pubmed-meshheading:15608060-Ethylmaleimide,
pubmed-meshheading:15608060-Gene Transfer Techniques,
pubmed-meshheading:15608060-Genotype,
pubmed-meshheading:15608060-Ligands,
pubmed-meshheading:15608060-Mice,
pubmed-meshheading:15608060-Mice, Transgenic,
pubmed-meshheading:15608060-Models, Biological,
pubmed-meshheading:15608060-Molecular Sequence Data,
pubmed-meshheading:15608060-Mutagenesis,
pubmed-meshheading:15608060-N-Ethylmaleimide-Sensitive Proteins,
pubmed-meshheading:15608060-Nuclear Proteins,
pubmed-meshheading:15608060-Peptides,
pubmed-meshheading:15608060-Phosphorylation,
pubmed-meshheading:15608060-Protein Kinase C,
pubmed-meshheading:15608060-Protein Structure, Tertiary,
pubmed-meshheading:15608060-Purkinje Cells,
pubmed-meshheading:15608060-Receptors, AMPA,
pubmed-meshheading:15608060-Synapses,
pubmed-meshheading:15608060-Time Factors,
pubmed-meshheading:15608060-Vesicular Transport Proteins
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pubmed:year |
2004
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pubmed:articleTitle |
N-ethylmaleimide-sensitive factor is required for the synaptic incorporation and removal of AMPA receptors during cerebellar long-term depression.
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pubmed:affiliation |
Howard Hughes Medical Institute and Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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