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Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts: implications for neuromodulation.

Brain-derived neurotrophic factor (BDNF) signaling is critical for neuronal development and transmission. Recruitment of TrkB receptors to lipid rafts has been shown to be necessary for the activation of specific signaling pathways and modulation of neurotransmitter release by BDNF. Since TrkB recep... Full description

Journal Title: The Journal of neuroscience : the official journal of the Society for Neuroscience June 23, 2010, Vol.30(25), pp.8468-8480
Main Author: Assaife-Lopes, Natália
Other Authors: Sousa, Vasco C , Pereira, Daniela B , Ribeiro, Joaquim A , Chao, Moses V , Sebastião, Ana M
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1529-2401 ; DOI: 10.1523/JNEUROSCI.5695-09.2010
Link: http://search.proquest.com/docview/733305812/?pq-origsite=primo
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title: Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts: implications for neuromodulation.
format: Article
creator:
  • Assaife-Lopes, Natália
  • Sousa, Vasco C
  • Pereira, Daniela B
  • Ribeiro, Joaquim A
  • Chao, Moses V
  • Sebastião, Ana M
subjects:
  • Adenosine–Analogs & Derivatives
  • Analysis of Variance–Pharmacology
  • Animals–Metabolism
  • Blotting, Western–Pharmacology
  • Brain-Derived Neurotrophic Factor–Metabolism
  • Cells, Cultured–Metabolism
  • Clathrin–Drug Effects
  • Cyclic Amp-Dependent Protein Kinases–Drug Effects
  • Endocytosis–Metabolism
  • Hippocampus–Drug Effects
  • Immunohistochemistry–Drug Effects
  • Long-Term Potentiation–Metabolism
  • Membrane Microdomains–Cytology
  • Neurons–Drug Effects
  • Phenethylamines–Metabolism
  • Phosphorylation–Pharmacology
  • Protein Transport–Drug Effects
  • Radioligand Assay–Drug Effects
  • Rats
ispartof: The Journal of neuroscience : the official journal of the Society for Neuroscience, June 23, 2010, Vol.30(25), pp.8468-8480
description: Brain-derived neurotrophic factor (BDNF) signaling is critical for neuronal development and transmission. Recruitment of TrkB receptors to lipid rafts has been shown to be necessary for the activation of specific signaling pathways and modulation of neurotransmitter release by BDNF. Since TrkB receptors are known to be modulated by adenosine A(2A) receptor activation, we hypothesized that activation of A(2A) receptors could influence TrkB receptor localization among different membrane microdomains. We found that adenosine A(2A) receptor agonists increased the levels of TrkB receptors in the lipid raft fraction of cortical membranes and potentiated BDNF-induced augmentation of phosphorylated TrkB levels in lipid rafts. Blockade of the clathrin-mediated endocytosis with monodansylcadaverine (100 microm) did not modify the effects of the A(2A) receptor agonists but significantly impaired BDNF effects on TrkB recruitment to lipid rafts. The effect of A(2A) receptor activation in TrkB localization was mimicked by 5 microm forskolin, an adenylyl cyclase activator. Also, it was blocked by the PKA inhibitors Rp-cAMPs and PKI-(14-22), and by the Src-family kinase inhibitor PP2. Moreover, removal of endogenous adenosine or disruption of lipid rafts reduced BDNF stimulatory effects on glutamate release from cortical synaptosomes. Lipid raft integrity was also required for the effects of BDNF on hippocampal long-term potentiation at CA1 synapses. Our data demonstrate, for the first time, a BDNF-independent recruitment of TrkB receptors to lipid rafts induced by activation of adenosine A(2A) receptors, with functional consequences for TrkB phosphorylation and BDNF-induced modulation of neurotransmitter release and hippocampal plasticity.
language: eng
source:
identifier: E-ISSN: 1529-2401 ; DOI: 10.1523/JNEUROSCI.5695-09.2010
fulltext: fulltext
issn:
  • 15292401
  • 1529-2401
url: Link


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titleActivation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts: implications for neuromodulation.
creatorAssaife-Lopes, Natália ; Sousa, Vasco C ; Pereira, Daniela B ; Ribeiro, Joaquim A ; Chao, Moses V ; Sebastião, Ana M
contributorAssaife-Lopes, Natália (correspondence author) ; Assaife-Lopes, Natália (record owner)
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identifierE-ISSN: 1529-2401 ; DOI: 10.1523/JNEUROSCI.5695-09.2010
subjectAdenosine–Analogs & Derivatives ; Analysis of Variance–Pharmacology ; Animals–Metabolism ; Blotting, Western–Pharmacology ; Brain-Derived Neurotrophic Factor–Metabolism ; Cells, Cultured–Metabolism ; Clathrin–Drug Effects ; Cyclic Amp-Dependent Protein Kinases–Drug Effects ; Endocytosis–Metabolism ; Hippocampus–Drug Effects ; Immunohistochemistry–Drug Effects ; Long-Term Potentiation–Metabolism ; Membrane Microdomains–Cytology ; Neurons–Drug Effects ; Phenethylamines–Metabolism ; Phosphorylation–Pharmacology ; Protein Transport–Drug Effects ; Radioligand Assay–Drug Effects ; Rats
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descriptionBrain-derived neurotrophic factor (BDNF) signaling is critical for neuronal development and transmission. Recruitment of TrkB receptors to lipid rafts has been shown to be necessary for the activation of specific signaling pathways and modulation of neurotransmitter release by BDNF. Since TrkB receptors are known to be modulated by adenosine A(2A) receptor activation, we hypothesized that activation of A(2A) receptors could influence TrkB receptor localization among different membrane microdomains. We found that adenosine A(2A) receptor agonists increased the levels of TrkB receptors in the lipid raft fraction of cortical membranes and potentiated BDNF-induced augmentation of phosphorylated TrkB levels in lipid rafts. Blockade of the clathrin-mediated endocytosis with monodansylcadaverine (100 microm) did not modify the effects of the A(2A) receptor agonists but significantly impaired BDNF effects on TrkB recruitment to lipid rafts. The effect of A(2A) receptor activation in TrkB localization was mimicked by 5 microm forskolin, an adenylyl cyclase activator. Also, it was blocked by the PKA inhibitors Rp-cAMPs and PKI-(14-22), and by the Src-family kinase inhibitor PP2. Moreover, removal of endogenous adenosine or disruption of lipid rafts reduced BDNF stimulatory effects on glutamate release from cortical synaptosomes. Lipid raft integrity was also required for the effects of BDNF on hippocampal long-term potentiation at CA1 synapses. Our data demonstrate, for the first time, a BDNF-independent recruitment of TrkB receptors to lipid rafts induced by activation of adenosine A(2A) receptors, with functional consequences for TrkB phosphorylation and BDNF-induced modulation of neurotransmitter release and hippocampal plasticity.
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