Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation

Neural progenitor cells (NPCs) are self-renewing cells that give rise to the major cells in the nervous system and are considered to be the possible cell of origin of glioblastoma. The gap junction protein connexin43 (Cx43) is expressed by NPCs, exerting channel-dependent and -independent roles. We...

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Detalles Bibliográficos
Autores: Talaverón Aguilocho, Rocío, Rodríguez Matarredona, Esperanza, Herrera Lira, Alejandro, Medina, José M., Tabernero, Arantxa
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/103159
Acceso en línea:https://hdl.handle.net/11441/103159
https://doi.org/10.3390/ijms21228852
Access Level:acceso abierto
Palabra clave:neural progenitor cells
neurons
astrocytes
ß-catenin
glioma stem cells
connexin
neural precursors
Cx43
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spelling Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic DifferentiationTalaverón Aguilocho, RocíoRodríguez Matarredona, EsperanzaHerrera Lira, AlejandroMedina, José M.Tabernero, Arantxaneural progenitor cellsneuronsastrocytesß-cateninglioma stem cellsconnexinneural precursorsCx43Neural progenitor cells (NPCs) are self-renewing cells that give rise to the major cells in the nervous system and are considered to be the possible cell of origin of glioblastoma. The gap junction protein connexin43 (Cx43) is expressed by NPCs, exerting channel-dependent and -independent roles. We focused on one property of Cx43—its ability to inhibit Src, a key protein in brain development and oncogenesis. Because Src inhibition is carried out by the sequence 266–283 of the intracellular C terminus in Cx43, we used a cell-penetrating peptide containing this sequence, TAT-Cx43266–283, to explore its effects on postnatal subventricular zone NPCs. Our results show that TAT-Cx43266–283 inhibited Src activity and reduced NPC proliferation and survival promoted by epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2). In differentiation conditions, TAT-Cx43266–283 increased astrocyte differentiation at the expense of neuronal differentiation, which coincided with a reduction in Src activity and β-catenin expression. We propose that Cx43, through the region 266–283, reduces Src activity, leading to disruption of EGF and FGF-2 signaling and to down-regulation of β-catenin with effects on proliferation and differentiation. Our data indicate that the inhibition of Src might contribute to the complex role of Cx43 in NPCs and open new opportunities for further research in gliomagenesis.España Ministerio de Ciencia, Innovación y Universidades, Spain, FEDER RTI2018-099873-B-I00 (A.T.) and PGC20185-094654-B-100FisiologíaMinisterio de Ciencia, Innovación y Universidades (MICINN). España2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/103159https://doi.org/10.3390/ijms21228852reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésInternational Journal of Molecular Science, 21 (22)RTI2018-099873-B-I00 (A.T.) and PGC20185-094654-B-100http://dx.doi.org/10.3390/ijms21228852info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1031592026-06-17T12:51:07Z
dc.title.none.fl_str_mv Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation
title Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation
spellingShingle Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation
Talaverón Aguilocho, Rocío
neural progenitor cells
neurons
astrocytes
ß-catenin
glioma stem cells
connexin
neural precursors
Cx43
title_short Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation
title_full Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation
title_fullStr Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation
title_full_unstemmed Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation
title_sort Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation
dc.creator.none.fl_str_mv Talaverón Aguilocho, Rocío
Rodríguez Matarredona, Esperanza
Herrera Lira, Alejandro
Medina, José M.
Tabernero, Arantxa
author Talaverón Aguilocho, Rocío
author_facet Talaverón Aguilocho, Rocío
Rodríguez Matarredona, Esperanza
Herrera Lira, Alejandro
Medina, José M.
Tabernero, Arantxa
author_role author
author2 Rodríguez Matarredona, Esperanza
Herrera Lira, Alejandro
Medina, José M.
Tabernero, Arantxa
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Fisiología
Ministerio de Ciencia, Innovación y Universidades (MICINN). España
dc.subject.none.fl_str_mv neural progenitor cells
neurons
astrocytes
ß-catenin
glioma stem cells
connexin
neural precursors
Cx43
topic neural progenitor cells
neurons
astrocytes
ß-catenin
glioma stem cells
connexin
neural precursors
Cx43
description Neural progenitor cells (NPCs) are self-renewing cells that give rise to the major cells in the nervous system and are considered to be the possible cell of origin of glioblastoma. The gap junction protein connexin43 (Cx43) is expressed by NPCs, exerting channel-dependent and -independent roles. We focused on one property of Cx43—its ability to inhibit Src, a key protein in brain development and oncogenesis. Because Src inhibition is carried out by the sequence 266–283 of the intracellular C terminus in Cx43, we used a cell-penetrating peptide containing this sequence, TAT-Cx43266–283, to explore its effects on postnatal subventricular zone NPCs. Our results show that TAT-Cx43266–283 inhibited Src activity and reduced NPC proliferation and survival promoted by epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2). In differentiation conditions, TAT-Cx43266–283 increased astrocyte differentiation at the expense of neuronal differentiation, which coincided with a reduction in Src activity and β-catenin expression. We propose that Cx43, through the region 266–283, reduces Src activity, leading to disruption of EGF and FGF-2 signaling and to down-regulation of β-catenin with effects on proliferation and differentiation. Our data indicate that the inhibition of Src might contribute to the complex role of Cx43 in NPCs and open new opportunities for further research in gliomagenesis.
publishDate 2020
dc.date.none.fl_str_mv 2020
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/11441/103159
https://doi.org/10.3390/ijms21228852
url https://hdl.handle.net/11441/103159
https://doi.org/10.3390/ijms21228852
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv International Journal of Molecular Science, 21 (22)
RTI2018-099873-B-I00 (A.T.) and PGC20185-094654-B-100
http://dx.doi.org/10.3390/ijms21228852
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,198674

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