Characterization of alternatively spliced isoforms of AMPA receptor subunits encoding truncated receptors
Autor(a) principal: | |
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Data de Publicação: | 2008 |
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/10316/5314 https://doi.org/10.1016/j.mcn.2007.10.008 |
Resumo: | Glutamate receptors of the [alpha]-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type play an important role in synaptic plasticity and contribute to cell death under excitotoxic conditions. AMPA receptors form heterotetramers of four homologous subunits (GluR1-4), which exist in two functionally different isoforms, flip and flop, generated by alternative splicing. We identified transcripts for alternatively spliced isoforms of AMPA receptor subunits which lack both the flip and the flop exons, in hippocampal and retinal cultures. These transcripts originate AMPA receptor subunits lacking the flip/flop cassette, the fourth transmembrane domain and the intracellular C-terminus. Truncated GluR1 associates with full-length GluR1 and exerts a dominant negative effect, giving rise to non-functional receptors. Moreover, truncated GluR1 reaches the cell surface, but is not efficiently targeted to the synapse. Hippocampal neuronal transfection with truncated GluR1 resulted in a significant reduction in apoptotic neuronal death triggered by toxic concentrations of glutamate. Furthermore, mRNA coding for the truncated subunits is consistently detected in some regions of the brain in epileptic rats and in hippocampal neurons submitted to toxic concentrations of glutamate. The existence of truncated AMPA receptor subunits may constitute an intrinsic neuroprotective mechanism. |
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Characterization of alternatively spliced isoforms of AMPA receptor subunits encoding truncated receptorsFlip/flopDominant negativeExcitotoxicityNeuroprotectionSynaptic targetingGlutamate receptors of the [alpha]-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type play an important role in synaptic plasticity and contribute to cell death under excitotoxic conditions. AMPA receptors form heterotetramers of four homologous subunits (GluR1-4), which exist in two functionally different isoforms, flip and flop, generated by alternative splicing. We identified transcripts for alternatively spliced isoforms of AMPA receptor subunits which lack both the flip and the flop exons, in hippocampal and retinal cultures. These transcripts originate AMPA receptor subunits lacking the flip/flop cassette, the fourth transmembrane domain and the intracellular C-terminus. Truncated GluR1 associates with full-length GluR1 and exerts a dominant negative effect, giving rise to non-functional receptors. Moreover, truncated GluR1 reaches the cell surface, but is not efficiently targeted to the synapse. Hippocampal neuronal transfection with truncated GluR1 resulted in a significant reduction in apoptotic neuronal death triggered by toxic concentrations of glutamate. Furthermore, mRNA coding for the truncated subunits is consistently detected in some regions of the brain in epileptic rats and in hippocampal neurons submitted to toxic concentrations of glutamate. The existence of truncated AMPA receptor subunits may constitute an intrinsic neuroprotective mechanism.http://www.sciencedirect.com/science/article/B6WNB-4PYP729-5/1/d6edd52e3e9022fd10b107a7f9e3bba92008info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/5314http://hdl.handle.net/10316/5314https://doi.org/10.1016/j.mcn.2007.10.008engMolecular and Cellular Neuroscience. 37:2 (2008) 323-334Gomes, André R.Ferreira, Joana S.Paternain, Ana V.Lerma, JuanDuarte, Carlos B.Carvalho, Ana Luísainfo: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:RCAAP2020-11-06T16:49:15ZPortal AgregadorONG |
dc.title.none.fl_str_mv |
Characterization of alternatively spliced isoforms of AMPA receptor subunits encoding truncated receptors |
title |
Characterization of alternatively spliced isoforms of AMPA receptor subunits encoding truncated receptors |
spellingShingle |
Characterization of alternatively spliced isoforms of AMPA receptor subunits encoding truncated receptors Gomes, André R. Flip/flop Dominant negative Excitotoxicity Neuroprotection Synaptic targeting |
title_short |
Characterization of alternatively spliced isoforms of AMPA receptor subunits encoding truncated receptors |
title_full |
Characterization of alternatively spliced isoforms of AMPA receptor subunits encoding truncated receptors |
title_fullStr |
Characterization of alternatively spliced isoforms of AMPA receptor subunits encoding truncated receptors |
title_full_unstemmed |
Characterization of alternatively spliced isoforms of AMPA receptor subunits encoding truncated receptors |
title_sort |
Characterization of alternatively spliced isoforms of AMPA receptor subunits encoding truncated receptors |
author |
Gomes, André R. |
author_facet |
Gomes, André R. Ferreira, Joana S. Paternain, Ana V. Lerma, Juan Duarte, Carlos B. Carvalho, Ana Luísa |
author_role |
author |
author2 |
Ferreira, Joana S. Paternain, Ana V. Lerma, Juan Duarte, Carlos B. Carvalho, Ana Luísa |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Gomes, André R. Ferreira, Joana S. Paternain, Ana V. Lerma, Juan Duarte, Carlos B. Carvalho, Ana Luísa |
dc.subject.por.fl_str_mv |
Flip/flop Dominant negative Excitotoxicity Neuroprotection Synaptic targeting |
topic |
Flip/flop Dominant negative Excitotoxicity Neuroprotection Synaptic targeting |
description |
Glutamate receptors of the [alpha]-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type play an important role in synaptic plasticity and contribute to cell death under excitotoxic conditions. AMPA receptors form heterotetramers of four homologous subunits (GluR1-4), which exist in two functionally different isoforms, flip and flop, generated by alternative splicing. We identified transcripts for alternatively spliced isoforms of AMPA receptor subunits which lack both the flip and the flop exons, in hippocampal and retinal cultures. These transcripts originate AMPA receptor subunits lacking the flip/flop cassette, the fourth transmembrane domain and the intracellular C-terminus. Truncated GluR1 associates with full-length GluR1 and exerts a dominant negative effect, giving rise to non-functional receptors. Moreover, truncated GluR1 reaches the cell surface, but is not efficiently targeted to the synapse. Hippocampal neuronal transfection with truncated GluR1 resulted in a significant reduction in apoptotic neuronal death triggered by toxic concentrations of glutamate. Furthermore, mRNA coding for the truncated subunits is consistently detected in some regions of the brain in epileptic rats and in hippocampal neurons submitted to toxic concentrations of glutamate. The existence of truncated AMPA receptor subunits may constitute an intrinsic neuroprotective mechanism. |
publishDate |
2008 |
dc.date.none.fl_str_mv |
2008 |
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/10316/5314 http://hdl.handle.net/10316/5314 https://doi.org/10.1016/j.mcn.2007.10.008 |
url |
http://hdl.handle.net/10316/5314 https://doi.org/10.1016/j.mcn.2007.10.008 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Molecular and Cellular Neuroscience. 37:2 (2008) 323-334 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
aplication/PDF |
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 |
instname_str |
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) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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1777302654452498432 |