Pyk2 regulates MAMs and mitochondrial dynamics in hippocampal neurons

Pyk2 is a non-receptor tyrosine kinase enriched in hippocampal neurons, which can be activated by calcium-dependent mechanisms. In neurons, Pyk2 is mostly localised in the cytosol and dendritic shafts but can translocate to spines and/or to the nucleus. Here, we explore the function of a new localis...

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Authors: López-Molina, Laura, Fernández Irigoyen, Joaquín, Cifuentes-Díaz, Carmen, Alberch, Jordi, Girault, Jean Antoine, Santamaría Martínez, Enrique, Ginés, Silvia, Giralt, Albert
Format: article
Status:Published version
Publication Date:2022
Country:España
Institution:Universidad Pública de Navarra
Repository:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/43738
Online Access:https://hdl.handle.net/2454/43738
Access Level:Open access
Keyword:Calcium
ER-mitochondria contact sites
Hippocampus
Neuron
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spelling Pyk2 regulates MAMs and mitochondrial dynamics in hippocampal neuronsLópez-Molina, LauraFernández Irigoyen, JoaquínCifuentes-Díaz, CarmenAlberch, JordiGirault, Jean AntoineSantamaría Martínez, EnriqueGinés, SilviaGiralt, AlbertCalciumER-mitochondria contact sitesHippocampusNeuronPyk2 is a non-receptor tyrosine kinase enriched in hippocampal neurons, which can be activated by calcium-dependent mechanisms. In neurons, Pyk2 is mostly localised in the cytosol and dendritic shafts but can translocate to spines and/or to the nucleus. Here, we explore the function of a new localisation of Pyk2 in mitochondria-associated membranes (MAMs), a subdomain of ER-mitochondria surface that acts as a signalling hub in calcium regulation. To test the role of Pyk2 in MAMs’ calcium transport, we used full Pyk2 knockout mice (Pyk2−/−) for in vivo and in vitro studies. Here we report that Pyk2−/− hippocampal neurons present increased ER-mitochondrial contacts along with defective calcium homeostasis. We also show how the absence of Pyk2 modulates mitochondrial dynamics and morphology. Taken all together, our results point out that Pyk2 could be highly relevant in the modulation of ER-mitochondria calcium efflux, affecting in turn mitochondrial functionA.G. is a Ramón y Cajal fellow (RYC-2016¿19466) supported by a grant from Ministerio de Ciencia, Innovación y Universidades (RTI2018-094678-A-I00). RTI2018-094374-B-I00 to S.G., from Ministerio de Ciencia, Innovación y Universidades.MDPICiencias de la SaludOsasun Zientziak2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/ziphttps://hdl.handle.net/2454/43738reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarrainstname:Universidad Pública de NavarraInglésinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-094678-A-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-094374-B-I00© 2022 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) licensehttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:academica-e.unavarra.es:2454/437382026-06-17T12:41:47Z
dc.title.none.fl_str_mv Pyk2 regulates MAMs and mitochondrial dynamics in hippocampal neurons
title Pyk2 regulates MAMs and mitochondrial dynamics in hippocampal neurons
spellingShingle Pyk2 regulates MAMs and mitochondrial dynamics in hippocampal neurons
López-Molina, Laura
Calcium
ER-mitochondria contact sites
Hippocampus
Neuron
title_short Pyk2 regulates MAMs and mitochondrial dynamics in hippocampal neurons
title_full Pyk2 regulates MAMs and mitochondrial dynamics in hippocampal neurons
title_fullStr Pyk2 regulates MAMs and mitochondrial dynamics in hippocampal neurons
title_full_unstemmed Pyk2 regulates MAMs and mitochondrial dynamics in hippocampal neurons
title_sort Pyk2 regulates MAMs and mitochondrial dynamics in hippocampal neurons
dc.creator.none.fl_str_mv López-Molina, Laura
Fernández Irigoyen, Joaquín
Cifuentes-Díaz, Carmen
Alberch, Jordi
Girault, Jean Antoine
Santamaría Martínez, Enrique
Ginés, Silvia
Giralt, Albert
author López-Molina, Laura
author_facet López-Molina, Laura
Fernández Irigoyen, Joaquín
Cifuentes-Díaz, Carmen
Alberch, Jordi
Girault, Jean Antoine
Santamaría Martínez, Enrique
Ginés, Silvia
Giralt, Albert
author_role author
author2 Fernández Irigoyen, Joaquín
Cifuentes-Díaz, Carmen
Alberch, Jordi
Girault, Jean Antoine
Santamaría Martínez, Enrique
Ginés, Silvia
Giralt, Albert
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ciencias de la Salud
Osasun Zientziak
dc.subject.none.fl_str_mv Calcium
ER-mitochondria contact sites
Hippocampus
Neuron
topic Calcium
ER-mitochondria contact sites
Hippocampus
Neuron
description Pyk2 is a non-receptor tyrosine kinase enriched in hippocampal neurons, which can be activated by calcium-dependent mechanisms. In neurons, Pyk2 is mostly localised in the cytosol and dendritic shafts but can translocate to spines and/or to the nucleus. Here, we explore the function of a new localisation of Pyk2 in mitochondria-associated membranes (MAMs), a subdomain of ER-mitochondria surface that acts as a signalling hub in calcium regulation. To test the role of Pyk2 in MAMs’ calcium transport, we used full Pyk2 knockout mice (Pyk2−/−) for in vivo and in vitro studies. Here we report that Pyk2−/− hippocampal neurons present increased ER-mitochondrial contacts along with defective calcium homeostasis. We also show how the absence of Pyk2 modulates mitochondrial dynamics and morphology. Taken all together, our results point out that Pyk2 could be highly relevant in the modulation of ER-mitochondria calcium efflux, affecting in turn mitochondrial function
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2454/43738
url https://hdl.handle.net/2454/43738
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-094678-A-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-094374-B-I00
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/zip
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
instname:Universidad Pública de Navarra
instname_str Universidad Pública de Navarra
reponame_str Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
collection Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
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repository.mail.fl_str_mv
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