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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Detalles Bibliográficos
Autores: López-Molina, Laura, Fernández Irigoyen, Joaquín, Cifuentes-Díaz, Carmen, Alberch, Jordi, Girault, Jean Antoine, Santamaría Martínez, Enrique, Ginés, Silvia, Giralt, Albert
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/43738
Acceso en línea:https://hdl.handle.net/2454/43738
Access Level:acceso abierto
Palabra clave:Calcium
ER-mitochondria contact sites
Hippocampus
Neuron
Descripción
Sumario: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