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Glutamatergic stimulation induces GluN2B translation by the nitric oxide-Heme-Regulated eIF2α kinase in cortical neurons

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dc.contributor.author Ramos Fernández, Eva, 1984-
dc.contributor.author Tajes Orduña, Marta
dc.contributor.author Ill-Raga, Gerard, 1982-
dc.contributor.author Vargas, Lina M.
dc.contributor.author Busquets Garcia, Arnau, 1985-
dc.contributor.author Bosch Morató, Mònica, 1986-
dc.contributor.author Guivernau Almazán, Biuse, 1988-
dc.contributor.author Valls Comamala, Victòria, 1987-
dc.contributor.author Gomis González, Maria, 1988-
dc.contributor.author Grau, Cristina
dc.contributor.author Fandos, César
dc.contributor.author Rosen, Mark D.
dc.contributor.author Rabinowitz, Michael H.
dc.contributor.author Inestrosa, Nibaldo C.
dc.contributor.author Maldonado, Rafael, 1961-
dc.contributor.author Altafaj, Xavier
dc.contributor.author Ozaita Mintegui, Andrés, 1969-
dc.contributor.author Álvarez, Alejandra R.
dc.contributor.author Vicente García, Rubén, 1978-
dc.contributor.author Valverde, M. A. (Miguel Ángel), 1963-
dc.contributor.author Muñoz López, Francisco José, 1964-
dc.date.accessioned 2016-12-15T08:14:24Z
dc.date.available 2016-12-15T08:14:24Z
dc.date.issued 2016
dc.identifier.citation Ramos-Fernández E, Tajes M, Ill-Raga G, Vargas L, Busquets-García A, Bosch-Morató M, Guivernau B, Valls-Comamala V, Gomis M, Grau C, Fandos C, Rosen MD, Rabinowitz MH, Inestrosa N, Maldonado R, Altafaj X, Ozaita A, Alvarez A, Vicente R, Valverde MA, Muñoz FJ. Glutamatergic stimulation induces GluN2B translation by the nitric oxide-Heme-Regulated eIF2α kinase in cortical neurons. Oncotarget. 2016 Aug 19; 7(37): 58876-58892. DOI: 10.18632/oncotarget.11417
dc.identifier.issn 1949-2553
dc.identifier.uri http://hdl.handle.net/10230/27768
dc.description.abstract The activation of N-Methyl D-Aspartate Receptor (NMDAR) by glutamate is crucial in the nervous system function, particularly in memory and learning. NMDAR is composed by two GluN1 and two GluN2 subunits. GluN2B has been reported to participate in the prevalent NMDAR subtype at synapses, the GluN1/2A/2B. Here we studied the regulation of GluN2B expression in cortical neurons finding that glutamate up-regulates GluN2B translation through the action of nitric oxide (NO), which induces the phosphorylation of the eukaryotic translation initiation factor 2 α (eIF2α). It is a process mediated by the NO-heme-regulated eIF2α kinase (HRI), as the effect was avoided when a specific HRI inhibitor or a HRI small interfering RNA (siHRI) were used. We found that the expressed GluN2B co-localizes with PSD-95 at the postsynaptic ending, which strengthen the physiological relevance of the proposed mechanism. Moreover the receptors bearing GluN2B subunits upon NO stimulation are functional as high Ca2+ entry was measured and increases the co-localization between GluN2B and GluN1 subunits. In addition, the injection of the specific HRI inhibitor in mice produces a decrease in memory retrieval as tested by the Novel Object Recognition performance. Summarizing our data suggests that glutamatergic stimulation induces HRI activation by NO to trigger GluN2B expression and this process would be relevant to maintain postsynaptic activity in cortical neurons.
dc.description.sponsorship This work was supported by the Plan Estatal de I+D+I 2013-2016 and the ISCIII-Subdirección/nGeneral de Evaluación y Fomento de la Investigación (Grants PI13/00408; PI13/00135; Red HERACLES RD12/0042/0014) and FEDER Funds; the Spanish Ministry of Economy and Competitiveness (SAF2014-52228-R; SAF2015-69762-R; BFU2015-68568-P); MINECO (PCIN-2014-105); Fundació la Marató de TV3 (20134030 and 20140210); FONDECYT 3140355 (ERF),/n1120512 (AAR) and 3120015 (LVR)
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Impact Journals
dc.relation.ispartof Oncotarget. 2016 Aug 19;7(37):58876-92
dc.rights All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License
dc.rights.uri http://creativecommons.org/licenses/by/3.0/
dc.subject.other Sistema nerviós
dc.subject.other Bioquímica
dc.title Glutamatergic stimulation induces GluN2B translation by the nitric oxide-Heme-Regulated eIF2α kinase in cortical neurons
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.11417
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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