Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/5314
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dc.contributor.authorGomes, André R.-
dc.contributor.authorFerreira, Joana S.-
dc.contributor.authorPaternain, Ana V.-
dc.contributor.authorLerma, Juan-
dc.contributor.authorDuarte, Carlos B.-
dc.contributor.authorCarvalho, Ana Luísa-
dc.date.accessioned2008-09-01T15:40:07Z-
dc.date.available2008-09-01T15:40:07Z-
dc.date.issued2008en_US
dc.identifier.citationMolecular and Cellular Neuroscience. 37:2 (2008) 323-334en_US
dc.identifier.urihttp://hdl.handle.net/10316/5314-
dc.description.abstractGlutamate 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.en_US
dc.description.urihttp://www.sciencedirect.com/science/article/B6WNB-4PYP729-5/1/d6edd52e3e9022fd10b107a7f9e3bba9en_US
dc.format.mimetypeaplication/PDFen
dc.language.isoengeng
dc.rightsopenAccesseng
dc.subjectFlip/flopen_US
dc.subjectDominant negativeen_US
dc.subjectExcitotoxicityen_US
dc.subjectNeuroprotectionen_US
dc.subjectSynaptic targetingen_US
dc.titleCharacterization of alternatively spliced isoforms of AMPA receptor subunits encoding truncated receptorsen_US
dc.typearticleen_US
uc.controloAutoridadeSim-
item.languageiso639-1en-
item.grantfulltextopen-
item.fulltextCom Texto completo-
crisitem.author.deptFaculdade de Ciências e Tecnologia, Universidade de Coimbra-
crisitem.author.parentdeptUniversidade de Coimbra-
crisitem.author.researchunitCNC.IBILI-
crisitem.author.orcid0000-0002-1474-0208-
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais
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