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

Abstract Wnt 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...

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Autores principales:	Eva Ramos-Fernández, Macarena S. Arrázola, Carolina A. Oliva, Sebastián B. Arredondo, Lorena Varela-Nallar, Nibaldo C. Inestrosa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/390ac201791347b586eeab76239c7001
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spelling	oai:doaj.org-article:390ac201791347b586eeab76239c70012021-12-02T13:27:04ZWnt5a promotes hippocampal postsynaptic development and GluN2B-induced expression via the eIF2α HRI kinase10.1038/s41598-021-86708-y2045-2322https://doaj.org/article/390ac201791347b586eeab76239c70012021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86708-yhttps://doaj.org/toc/2045-2322Abstract Wnt 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.Eva Ramos-FernándezMacarena S. ArrázolaCarolina A. OlivaSebastián B. ArredondoLorena Varela-NallarNibaldo C. InestrosaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eva Ramos-Fernández Macarena S. Arrázola Carolina A. Oliva Sebastián B. Arredondo Lorena Varela-Nallar Nibaldo C. Inestrosa Wnt5a promotes hippocampal postsynaptic development and GluN2B-induced expression via the eIF2α HRI kinase
description	Abstract Wnt 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.
format	article
author	Eva Ramos-Fernández Macarena S. Arrázola Carolina A. Oliva Sebastián B. Arredondo Lorena Varela-Nallar Nibaldo C. Inestrosa
author_facet	Eva Ramos-Fernández Macarena S. Arrázola Carolina A. Oliva Sebastián B. Arredondo Lorena Varela-Nallar Nibaldo C. Inestrosa
author_sort	Eva Ramos-Fernández
title	Wnt5a promotes hippocampal postsynaptic development and GluN2B-induced expression via the eIF2α HRI kinase
title_short	Wnt5a promotes hippocampal postsynaptic development and GluN2B-induced expression via the eIF2α HRI kinase
title_full	Wnt5a promotes hippocampal postsynaptic development and GluN2B-induced expression via the eIF2α HRI kinase
title_fullStr	Wnt5a promotes hippocampal postsynaptic development and GluN2B-induced expression via the eIF2α HRI kinase
title_full_unstemmed	Wnt5a promotes hippocampal postsynaptic development and GluN2B-induced expression via the eIF2α HRI kinase
title_sort	wnt5a promotes hippocampal postsynaptic development and glun2b-induced expression via the eif2α hri kinase
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/390ac201791347b586eeab76239c7001
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Wnt5a promotes hippocampal postsynaptic development and GluN2B-induced expression via the eIF2α HRI kinase

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