DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden

The P2X7 receptor (P2X7R) stands out within the purinergic family as it has exclusive pharmacological and regulatory features, and it fulfills distinct roles depending on the type of stimulation and cellular environment. Tonic activation of P2X7R promotes cell proliferation, whereas sustained activa...

Full description

Bibliographic Details
Authors: Gil Redondo, Juan Carlos, Queipo García, María José, Trueba, Yaiza, Llorente Sáez, Celia, Serrano, Julia, Ortega De La O, Felipe, Gómez Villafuertes, María Rosa, Pérez Sen, Raquel, García Delicado, Esmerilda
Format: article
Publication Date:2023
Country:España
Institution:Universidad Complutense de Madrid (UCM)
Repository:Docta Complutense
Language:English
OAI Identifier:oai:docta.ucm.es:20.500.14352/103640
Online Access:https://hdl.handle.net/20.500.14352/103640
Access Level:Open access
Keyword:612.015
Astrocytes
Brain-derived neurotrophic factor
Dual-specifcity protein phosphatase 1
ERK signaling
Granule neurons
P2X7 nucleotide receptor
Veterinaria
3109 Ciencias Veterinarias
id ES_e8f2b0d41a8234c586f4b79b4bd04fda
oai_identifier_str oai:docta.ucm.es:20.500.14352/103640
network_acronym_str ES
network_name_str España
repository_id_str
spelling DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of EdenGil Redondo, Juan CarlosQueipo García, María JoséTrueba, YaizaLlorente Sáez, CeliaSerrano, JuliaOrtega De La O, FelipeGómez Villafuertes, María RosaPérez Sen, RaquelGarcía Delicado, Esmerilda612.015AstrocytesBrain-derived neurotrophic factorDual-specifcity protein phosphatase 1ERK signalingGranule neuronsP2X7 nucleotide receptorVeterinaria3109 Ciencias VeterinariasThe P2X7 receptor (P2X7R) stands out within the purinergic family as it has exclusive pharmacological and regulatory features, and it fulfills distinct roles depending on the type of stimulation and cellular environment. Tonic activation of P2X7R promotes cell proliferation, whereas sustained activation is associated with cell death. Yet strikingly, prolonged P2X7R activation in rat cerebellar granule neurons and astrocytes does not affect cell survival. The intracellular pathways activated by P2X7Rs involve proteins like MAPKs, ERK1/2 and p38, and interactions with growth factor receptors could explain their behavior in populations of rat cerebellar cells. In this study, we set out to characterize the intracellular mechanisms through which P2X7Rs and Trk receptors, EGFR (epidermal growth factor receptor) and BDNFR (brain-derived neurotrophic factor receptor), regulate the dual-specificity phosphatase DUSP1. In cerebellar astrocytes, the regulation of DUSP1 expression by P2X7R depends on ERK and p38 activation. EGFR stimulation can also induce DUSP1 expression, albeit less strongly than P2X7R. Conversely, EGF was virtually ineffective in regulating DUSP1 in granule neurons, a cell type in which BDNF is the main regulator of DUSP1 expression and P2X7R only induces a mild response. Indeed, the regulation of DUSP1 elicited by BDNF reflects the balance between both transcriptional and post-transcriptional mechanisms. Importantly, when the regulation of DUSP1 expression is compromised, the viability of both astrocytes and neurons is impaired, suggesting this phosphatase is essential to maintain proper cell cytoarchitecture and functioning.SpringerUniversidad Complutense de Madrid20232023-09-3020232023-09-30journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/103640reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengMCIU PID219 09-155RB-100UCM-CAM PR65 19–22453open accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1036402026-06-02T12:44:21Z
dc.title.none.fl_str_mv DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden
title DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden
spellingShingle DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden
Gil Redondo, Juan Carlos
612.015
Astrocytes
Brain-derived neurotrophic factor
Dual-specifcity protein phosphatase 1
ERK signaling
Granule neurons
P2X7 nucleotide receptor
Veterinaria
3109 Ciencias Veterinarias
title_short DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden
title_full DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden
title_fullStr DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden
title_full_unstemmed DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden
title_sort DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden
dc.creator.none.fl_str_mv Gil Redondo, Juan Carlos
Queipo García, María José
Trueba, Yaiza
Llorente Sáez, Celia
Serrano, Julia
Ortega De La O, Felipe
Gómez Villafuertes, María Rosa
Pérez Sen, Raquel
García Delicado, Esmerilda
author Gil Redondo, Juan Carlos
author_facet Gil Redondo, Juan Carlos
Queipo García, María José
Trueba, Yaiza
Llorente Sáez, Celia
Serrano, Julia
Ortega De La O, Felipe
Gómez Villafuertes, María Rosa
Pérez Sen, Raquel
García Delicado, Esmerilda
author_role author
author2 Queipo García, María José
Trueba, Yaiza
Llorente Sáez, Celia
Serrano, Julia
Ortega De La O, Felipe
Gómez Villafuertes, María Rosa
Pérez Sen, Raquel
García Delicado, Esmerilda
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 612.015
Astrocytes
Brain-derived neurotrophic factor
Dual-specifcity protein phosphatase 1
ERK signaling
Granule neurons
P2X7 nucleotide receptor
Veterinaria
3109 Ciencias Veterinarias
topic 612.015
Astrocytes
Brain-derived neurotrophic factor
Dual-specifcity protein phosphatase 1
ERK signaling
Granule neurons
P2X7 nucleotide receptor
Veterinaria
3109 Ciencias Veterinarias
description The P2X7 receptor (P2X7R) stands out within the purinergic family as it has exclusive pharmacological and regulatory features, and it fulfills distinct roles depending on the type of stimulation and cellular environment. Tonic activation of P2X7R promotes cell proliferation, whereas sustained activation is associated with cell death. Yet strikingly, prolonged P2X7R activation in rat cerebellar granule neurons and astrocytes does not affect cell survival. The intracellular pathways activated by P2X7Rs involve proteins like MAPKs, ERK1/2 and p38, and interactions with growth factor receptors could explain their behavior in populations of rat cerebellar cells. In this study, we set out to characterize the intracellular mechanisms through which P2X7Rs and Trk receptors, EGFR (epidermal growth factor receptor) and BDNFR (brain-derived neurotrophic factor receptor), regulate the dual-specificity phosphatase DUSP1. In cerebellar astrocytes, the regulation of DUSP1 expression by P2X7R depends on ERK and p38 activation. EGFR stimulation can also induce DUSP1 expression, albeit less strongly than P2X7R. Conversely, EGF was virtually ineffective in regulating DUSP1 in granule neurons, a cell type in which BDNF is the main regulator of DUSP1 expression and P2X7R only induces a mild response. Indeed, the regulation of DUSP1 elicited by BDNF reflects the balance between both transcriptional and post-transcriptional mechanisms. Importantly, when the regulation of DUSP1 expression is compromised, the viability of both astrocytes and neurons is impaired, suggesting this phosphatase is essential to maintain proper cell cytoarchitecture and functioning.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-09-30
2023
2023-09-30
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/103640
url https://hdl.handle.net/20.500.14352/103640
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv MCIU PID219 09-155RB-100
UCM-CAM PR65 19–22453
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869422985511698432
score 15.300719

Similar Items