Wnt5a promotes hippocampal postsynaptic development and GluN2B-induced expression via the eIF2α HRI kinase

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dc.contributor.authorRamos-Fernández, E.
dc.contributor.authorArrázola, M.S.
dc.contributor.authorOliva, C.A.
dc.contributor.authorArredondo, S.B.
dc.contributor.authorVarela-Nallar, L.
dc.contributor.authorInestrosa, N.C.
dc.date.accessioned2021-05-11T13:43:24Z
dc.date.available2021-05-11T13:43:24Z
dc.date.issued2021-12
dc.descriptionIndexación Scopuses
dc.description.abstractWnt signaling plays a key role in neurodevelopment and neuronal maturation. Specifically, Wnt5a stimulates postsynaptic assemblies, increases glutamatergic neurotransmission and, through calcium signaling, generates nitric oxide (NO). Trying to unveil the molecular pathway triggering these postsynaptic effects, we found that Wnt5a treatment induces a time-dependent increases in the length of the postsynaptic density (PSD), elicits novel synaptic contacts and facilitates F-actin flow both in in vitro and ex vivo models. These effects were partially abolished by the inhibition of the Heme-regulated eukaryotic initiation factor 2α (HRI) kinase, a kinase which phosphorylates the initiation translational factor eIF2α. When phosphorylated, eIF2α normally avoids the translation of proteins not needed during stress conditions, in order to avoid unnecessary energetic expenses. However, phosphorylated eIF2α promotes the translation of some proteins with more than one open reading frame in its 5′ untranslated region. One of these proteins targeted by Wnt-HRI-eIF2α mediated translation is the GluN2B subunit of the NMDA receptor. The identified increase in GluN2B expression correlated with increased NMDA receptor function. Considering that NMDA receptors are crucial for excitatory synaptic transmission, the molecular pathway described here contributes to the understanding of the fast and plastic translational mechanisms activated during learning and memory processes. © 2021, The Author(s).es
dc.description.urihttps://www-nature-com.recursosbiblioteca.unab.cl/articles/s41598-021-86708-y
dc.identifier.citationScientific Reports Volume 11, Issue 1, December 2021, Article number 7395es
dc.identifier.doi10.1038/s41598-021-86708-y
dc.identifier.issn20452322
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/18823
dc.language.isoenes
dc.publisherNature Researches
dc.subjectProtein Phosphatase 1es
dc.subjectNeurabines
dc.subjectPhospholambanes
dc.titleWnt5a promotes hippocampal postsynaptic development and GluN2B-induced expression via the eIF2α HRI kinasees
dc.typeArtículoes
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