Source:http://linkedlifedata.com/resource/pubmed/id/17394529
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2007-6-4
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pubmed:abstractText |
Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are essential regulators of synaptic function in the adult CNS. A TrkB-mediated effect at excitatory synapses is enhancement of NMDA receptor (NMDA-R)-mediated currents. Recently, opposing effects of TrkB and the pan-neurotrophin receptor p75(NTR) on long-term synaptic depression and long-term potentiation have been reported in the hippocampus. To further study the regulation of NMDA-Rs by neurotrophin receptors in their native protein environment, we micro-transplanted rat forebrain post-synaptic densities (PSDs) into Xenopus oocytes. One-minute incubations of oocytes with BDNF led to dual effects on NMDA-R currents: either TrkB-dependent potentiation or TrkB-independent inhibition were observed. Pro-nerve growth factor, a ligand for p75(NTR) but not for TrkB, produced a reversible, dose-dependent, TrkB-independent and p75(NTR)-dependent inhibition of NMDA-Rs. Fractionation experiments showed that p75(NTR) is highly enriched in the PSD protein fraction. Immunoprecipitation and pull-down experiments further revealed that p75(NTR) is a core component of the PSD, where it interacts with the PDZ3 domain of the scaffolding protein SAP90/PSD-95. Our data provide striking evidence for a rapid inhibitory effect of p75(NTR) on NMDA-R currents that antagonizes TrkB-mediated NMDA-R potentiation. These opposing mechanisms might be present in a large proportion of forebrain synapses and may contribute importantly to synaptic plasticity.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Brain-Derived Neurotrophic Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Nerve Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, trkB,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurotransmitter
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-3042
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pubmed:author |
pubmed-author:BronfmanFranciscaF,
pubmed-author:CalderónRodrigoR,
pubmed-author:FalconRominaR,
pubmed-author:GarnerCraig CCC,
pubmed-author:GundelfingerEckart DED,
pubmed-author:HeumannRolfR,
pubmed-author:MarengoJuan JoséJJ,
pubmed-author:SaavedraVerónicaV,
pubmed-author:SandovalMauricioM,
pubmed-author:SandovalRodrigoR,
pubmed-author:SmallaKarl-HeinzKH,
pubmed-author:SpilkerChristinaC,
pubmed-author:ThomasUlrichU,
pubmed-author:WynekenUrsulaU
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pubmed:issnType |
Print
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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 |
1672-84
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17394529-Animals,
pubmed-meshheading:17394529-Brain-Derived Neurotrophic Factor,
pubmed-meshheading:17394529-Female,
pubmed-meshheading:17394529-Immunoprecipitation,
pubmed-meshheading:17394529-Neuronal Plasticity,
pubmed-meshheading:17394529-Oocytes,
pubmed-meshheading:17394529-Protein Precursors,
pubmed-meshheading:17394529-Rats,
pubmed-meshheading:17394529-Rats, Sprague-Dawley,
pubmed-meshheading:17394529-Receptor, Nerve Growth Factor,
pubmed-meshheading:17394529-Receptor, trkB,
pubmed-meshheading:17394529-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:17394529-Receptors, Neurotransmitter,
pubmed-meshheading:17394529-Synaptic Membranes,
pubmed-meshheading:17394529-Xenopus laevis
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pubmed:year |
2007
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pubmed:articleTitle |
Antagonistic effects of TrkB and p75(NTR) on NMDA receptor currents in post-synaptic densities transplanted into Xenopus oocytes.
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pubmed:affiliation |
Laboratorio de Neurociencias, Universidad de Los Andes, Santiago, Chile.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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