Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts : implications for neuromodulation
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , , , |
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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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 instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134205000548352 |