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rdf:type |
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lifeskim:mentions |
umls-concept:C0027882,
umls-concept:C0033640,
umls-concept:C0080093,
umls-concept:C0085862,
umls-concept:C0086982,
umls-concept:C0205314,
umls-concept:C0521119,
umls-concept:C0530778,
umls-concept:C0596235,
umls-concept:C0679622,
umls-concept:C1299583,
umls-concept:C1549571,
umls-concept:C1608386
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pubmed:issue |
48
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pubmed:dateCreated |
2004-12-2
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pubmed:abstractText |
The specification and organization of glutamatergic synaptic transmission require the coordinated interaction among glutamate receptors and their synaptic adaptor proteins closely assembled in the postsynaptic density (PSD). Here we investigated the interaction between NMDA receptors and metabotropic glutamate receptor 5 (mGluR5) in the integral regulation of extracellular signal-regulated protein kinase (ERK) and gene expression in cultured rat striatal neurons. We found that coapplication of NMDA and the mGluR5 agonist (S)-3,5-dihydroxyphenylglycine synergistically increased ERK phosphorylation. Interestingly, the synergistic increase in ERK phosphorylation was dependent on the cross talk between NMDA receptor-associated synaptic adaptor protein PSD-95 and the mGluR5-linked adaptor protein Homer1b/c but not on the conventional Ca2+ signaling derived from NMDA receptors (Ca2+ influx) and mGluR5 (intracellular Ca2+ release). This was demonstrated by the findings that the synergistic phosphorylation of ERK induced by coactivation of NMDA receptors and mGluR5 was blocked by either a Tat peptide that disrupts NMDA receptor/PSD-95 binding or small interfering RNAs that selectively reduce cellular levels of Homer1b/c. Furthermore, ERK activated through this PSD-95/Homer1b/c-dependent and Ca2+-independent pathway was able to phosphorylate the two key transcription factors Elk-1 and cAMP response element-binding protein, which further leads to facilitation of c-Fos expression. Together, we have identified a novel Ca2+-independent signaling pathway to ERK by the synergistic interaction of NMDA receptors and mGluR5 via their adaptor proteins in the PSD of neurons, which underlies a synapse-to-nucleus communication important for the transcriptional regulation.
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pubmed:grant |
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pubmed:commentsCorrections |
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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/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Carbazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Diglycerides,
http://linkedlifedata.com/resource/pubmed/chemical/Dlgh4 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Elk1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Go 6983,
http://linkedlifedata.com/resource/pubmed/chemical/Homer protein,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Methoxyhydroxyphenylglycol,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate,
http://linkedlifedata.com/resource/pubmed/chemical/N-methyl D-aspartate receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/NMDA receptor 2B,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase C beta,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Ro 31-8220,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/dihydroxyphenylethylene glycol,
http://linkedlifedata.com/resource/pubmed/chemical/ets-Domain Protein Elk-1,
http://linkedlifedata.com/resource/pubmed/chemical/postsynaptic density proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10846-57
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15574735-Animals,
pubmed-meshheading:15574735-Calcium,
pubmed-meshheading:15574735-Rats,
pubmed-meshheading:15574735-Sodium,
pubmed-meshheading:15574735-Neurons,
pubmed-meshheading:15574735-Corpus Striatum,
pubmed-meshheading:15574735-Phosphorylation,
pubmed-meshheading:15574735-Indoles,
pubmed-meshheading:15574735-Carbazoles,
pubmed-meshheading:15574735-Synapses,
pubmed-meshheading:15574735-Cell Nucleus,
pubmed-meshheading:15574735-Membrane Proteins,
pubmed-meshheading:15574735-Ion Transport,
pubmed-meshheading:15574735-Nerve Tissue Proteins,
pubmed-meshheading:15574735-Isoenzymes,
pubmed-meshheading:15574735-Enzyme Activation,
pubmed-meshheading:15574735-Diglycerides,
pubmed-meshheading:15574735-Transcription, Genetic,
pubmed-meshheading:15574735-Carrier Proteins,
pubmed-meshheading:15574735-Gene Expression Regulation,
pubmed-meshheading:15574735-Calcium Signaling,
pubmed-meshheading:15574735-Signal Transduction,
pubmed-meshheading:15574735-Methoxyhydroxyphenylglycol,
pubmed-meshheading:15574735-DNA-Binding Proteins,
pubmed-meshheading:15574735-Type C Phospholipases,
pubmed-meshheading:15574735-Protein Processing, Post-Translational,
pubmed-meshheading:15574735-Transcription Factors,
pubmed-meshheading:15574735-N-Methylaspartate
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