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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Autores: Talaverón Aguilocho, Rocío, Matarredona, Esperanza R., Herrera, Alejandro, Medina Jiménez, José María, Tabernero Urbieta, María Aránzazu
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2020
País:España
Recursos:Universidad de Salamanca (USAL)
Repositório:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/154965
Acesso em linha:http://hdl.handle.net/10366/154965
Access Level:Acceso aberto
Palavra-chave:Cx43
astrocytes
connexin
glioma stem cells
neural precursors
neural progenitor cells
neurons
ß-catenin
Glioma
beta Catenin
Cells
Neurons
Connexins
Astrocytes
2411 Fisiología Humana
2490 Neurociencias
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oai_identifier_str oai:gredos.usal.es:10366/154965
network_acronym_str ES
network_name_str España
repository_id_str
spelling Connexin43 Region 266–283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic DifferentiationTalaverón Aguilocho, RocíoMatarredona, Esperanza R.Herrera, AlejandroMedina Jiménez, José MaríaTabernero Urbieta, María AránzazuCx43astrocytesconnexinglioma stem cellsneural precursorsneural progenitor cellsneuronsß-cateninGliomabeta CateninCellsNeuronsConnexinsAstrocytes2411 Fisiología Humana2490 NeurocienciasNeural 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.FEDER RTI2018-099873-B-I00/Ministerio de Ciencia, Innovación y Universidades Rocío Talaverón fellowship/Fundación Científica Asociación Española Contra el Cáncer PGC20185-094654-B-100/Ministerio de Ciencia, Innovación y Universidades202420242020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10366/154965reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)Inglésinfo:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1549652026-06-07T06:28:51Z
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
Cx43
astrocytes
connexin
glioma stem cells
neural precursors
neural progenitor cells
neurons
ß-catenin
Glioma
beta Catenin
Cells
Neurons
Connexins
Astrocytes
2411 Fisiología Humana
2490 Neurociencias
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
Matarredona, Esperanza R.
Herrera, Alejandro
Medina Jiménez, José María
Tabernero Urbieta, María Aránzazu
author Talaverón Aguilocho, Rocío
author_facet Talaverón Aguilocho, Rocío
Matarredona, Esperanza R.
Herrera, Alejandro
Medina Jiménez, José María
Tabernero Urbieta, María Aránzazu
author_role author
author2 Matarredona, Esperanza R.
Herrera, Alejandro
Medina Jiménez, José María
Tabernero Urbieta, María Aránzazu
author2_role author
author
author
author
dc.subject.none.fl_str_mv Cx43
astrocytes
connexin
glioma stem cells
neural precursors
neural progenitor cells
neurons
ß-catenin
Glioma
beta Catenin
Cells
Neurons
Connexins
Astrocytes
2411 Fisiología Humana
2490 Neurociencias
topic Cx43
astrocytes
connexin
glioma stem cells
neural precursors
neural progenitor cells
neurons
ß-catenin
Glioma
beta Catenin
Cells
Neurons
Connexins
Astrocytes
2411 Fisiología Humana
2490 Neurociencias
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
2024
2024
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 http://hdl.handle.net/10366/154965
url http://hdl.handle.net/10366/154965
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca
instname:Universidad de Salamanca (USAL)
instname_str Universidad de Salamanca (USAL)
reponame_str GREDOS. Repositorio Institucional de la Universidad de Salamanca
collection GREDOS. Repositorio Institucional de la Universidad de Salamanca
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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