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

Detalhes bibliográficos
Autor(a) principal: Assaife-Lopes, Natália
Data de Publicação: 2010
Outros Autores: Sousa, Vasco C., Pereira, Daniela B., Ribeiro, Joaquim A., Chao, Moses V., Sebastião, Ana M
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/6384
Resumo: Copyright © 2010 the authors
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spelling Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts : implications for neuromodulationAdenosine receptorsTrkBBDNFLipid raftsNeuromodulationCopyright © 2010 the authorsBrain-derived neurotrophic factor (BDNF) signaling is critical for neuronal development and transmission. Recruitment of TrkB receptors to lipid rafts has been hown 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 A2A receptor activation, we hypothesized that activation of A2A receptors could influence TrkB receptor localization among different membrane microdomains. We found that adenosine A2A 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(100µM) did not modify the effects of theA2A receptor agonists but significantly impairedBDNFeffects on TrkB recruitment to lipid rafts. The effect of A2A receptor activation in TrkB localization was mimicked by 5 µM 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 A2A receptors, with functional consequences for TrkB phosphorylation and BDNF-induced modulation of neurotransmitter release and hippocampal plasticity.Supported by Fundacão para a Ciência e a Tecnologia (SFRH/BD/21374/2005 for N.A.L., SFRH/BD/21359/2005 for V.C.S., and SFRH/BPD/11528/2002 for D.B.P.) and by the European Union [European Cooperation in Science and Technology (COST) COST B30 concerted action, Neural Regeneration and Plasticity (NEREPLAS)].Society for NeuroscienceRepositório da Universidade de LisboaAssaife-Lopes, NatáliaSousa, Vasco C.Pereira, Daniela B.Ribeiro, Joaquim A.Chao, Moses V.Sebastião, Ana M2012-05-29T13:04:45Z20102010-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/6384engThe Journal of Neuroscience, June 23, 2010 • 30(25):8468–84800270-6474info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T15:48:52Zoai:repositorio.ul.pt:10451/6384Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:31:32.083642Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts : implications for neuromodulation
title Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts : implications for neuromodulation
spellingShingle Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts : implications for neuromodulation
Assaife-Lopes, Natália
Adenosine receptors
TrkB
BDNF
Lipid rafts
Neuromodulation
title_short Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts : implications for neuromodulation
title_full Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts : implications for neuromodulation
title_fullStr Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts : implications for neuromodulation
title_full_unstemmed Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts : implications for neuromodulation
title_sort Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts : implications for neuromodulation
author Assaife-Lopes, Natália
author_facet Assaife-Lopes, Natália
Sousa, Vasco C.
Pereira, Daniela B.
Ribeiro, Joaquim A.
Chao, Moses V.
Sebastião, Ana M
author_role author
author2 Sousa, Vasco C.
Pereira, Daniela B.
Ribeiro, Joaquim A.
Chao, Moses V.
Sebastião, Ana M
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Assaife-Lopes, Natália
Sousa, Vasco C.
Pereira, Daniela B.
Ribeiro, Joaquim A.
Chao, Moses V.
Sebastião, Ana M
dc.subject.por.fl_str_mv Adenosine receptors
TrkB
BDNF
Lipid rafts
Neuromodulation
topic Adenosine receptors
TrkB
BDNF
Lipid rafts
Neuromodulation
description Copyright © 2010 the authors
publishDate 2010
dc.date.none.fl_str_mv 2010
2010-01-01T00:00:00Z
2012-05-29T13:04:45Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/6384
url http://hdl.handle.net/10451/6384
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv The Journal of Neuroscience, June 23, 2010 • 30(25):8468–8480
0270-6474
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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