Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of action

Autores
Perez, Maria Julia; Fernandez, Natalia Cristina; Pasquini, Juana Maria
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Oligodendrocytes are the cells producing the myelin membrane around the axons in the central nervous system and, although apotransferrin (aTf) is required for oligodendrocyte differentiation, the underlying mechanisms are not fully understood. Fyn tyrosine kinase, a member of the Src family of proteins, has been shown to play an important role in myelination by up-regulating the expression of myelin basic protein; however, a molecular link between aTf and Fyn kinase signaling pathway during oligodendrocytes differentiation has not been established yet. Our aim was to investigate whether Fyn kinase, MEK/ERK and PI3K/Akt signaling pathways are required for aTf-stimulation of oligodendrocyte differentiation and also to determine if the transferrin receptor is involved in these mechanisms. Treatment of primary cultures of oligodendroglial precursor cells with aTf leads to Fyn kinase activation by a mechanism that involves transferrin receptor. In turn, Fyn kinase activation promotes MEK-mediated transient phosphorylation of ERK1/2. On the other hand, transferrin receptor internalization also produces rapid and sustained activation of Akt, which involves phosphatidylinositol 3-kinase (PI3K) activation. Finally, aTf incorporated through clathrin-mediated endocytosis increases myelin basic protein, F3-contactin and β-tubulin through Fyn/MEK/ERK pathways, as well as an activation of the PI3K/Akt pathway. Our results also demonstrate that the activation of the pathways necessary for oligodendroglial precursor cell maturation is dependent on AP2 recruitment onto the plasma membrane for clathrin-mediated endocytosis of transferrin receptor.
Fil: Perez, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Quimica Biologica. Cátedra de Química Biológica Patológica; Argentina
Fil: Fernandez, Natalia Cristina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
Fil: Pasquini, Juana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Materia
Oligodendrocyte
Transferrin
Receptor-Internalization
Signalling
Fyn Tyrosine Kinase
Pi3k/Akt Pathway
Mek/Erk Pathways
Oligodendrocyte Differentiation And Transferrin
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/1898
Acceder
id CONICETDig_3027110ce3b0f8cd7cfdfb767234c341
oai_identifier_str oai:ri.conicet.gov.ar:11336/1898
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of actionPerez, Maria JuliaFernandez, Natalia CristinaPasquini, Juana MariaOligodendrocyteTransferrinReceptor-InternalizationSignallingFyn Tyrosine KinasePi3k/Akt PathwayMek/Erk PathwaysOligodendrocyte Differentiation And Transferrinhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Oligodendrocytes are the cells producing the myelin membrane around the axons in the central nervous system and, although apotransferrin (aTf) is required for oligodendrocyte differentiation, the underlying mechanisms are not fully understood. Fyn tyrosine kinase, a member of the Src family of proteins, has been shown to play an important role in myelination by up-regulating the expression of myelin basic protein; however, a molecular link between aTf and Fyn kinase signaling pathway during oligodendrocytes differentiation has not been established yet. Our aim was to investigate whether Fyn kinase, MEK/ERK and PI3K/Akt signaling pathways are required for aTf-stimulation of oligodendrocyte differentiation and also to determine if the transferrin receptor is involved in these mechanisms. Treatment of primary cultures of oligodendroglial precursor cells with aTf leads to Fyn kinase activation by a mechanism that involves transferrin receptor. In turn, Fyn kinase activation promotes MEK-mediated transient phosphorylation of ERK1/2. On the other hand, transferrin receptor internalization also produces rapid and sustained activation of Akt, which involves phosphatidylinositol 3-kinase (PI3K) activation. Finally, aTf incorporated through clathrin-mediated endocytosis increases myelin basic protein, F3-contactin and β-tubulin through Fyn/MEK/ERK pathways, as well as an activation of the PI3K/Akt pathway. Our results also demonstrate that the activation of the pathways necessary for oligodendroglial precursor cell maturation is dependent on AP2 recruitment onto the plasma membrane for clathrin-mediated endocytosis of transferrin receptor.Fil: Perez, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Quimica Biologica. Cátedra de Química Biológica Patológica; ArgentinaFil: Fernandez, Natalia Cristina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaFil: Pasquini, Juana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaElsevier2013-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/1898Perez, Maria Julia; Fernandez, Natalia Cristina; Pasquini, Juana Maria; Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of action; Elsevier; Experimental Neurology; 248; 10-2013; 262-2740014-4886enginfo:eu-repo/semantics/reference/url/info:eu-repo/semantics/reference es info:eu-repo/semantics/reference/pmid/23797152info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014488613001878#info:eu-repo/semantics/altIdentifier/doi/10.1016/j.expneurol.2013.06.014info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:15:57Zoai:ri.conicet.gov.ar:11336/1898instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:15:57.957CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of action
title Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of action
spellingShingle Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of action
Perez, Maria Julia
Oligodendrocyte
Transferrin
Receptor-Internalization
Signalling
Fyn Tyrosine Kinase
Pi3k/Akt Pathway
Mek/Erk Pathways
Oligodendrocyte Differentiation And Transferrin
title_short Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of action
title_full Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of action
title_fullStr Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of action
title_full_unstemmed Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of action
title_sort Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of action
dc.creator.none.fl_str_mv Perez, Maria Julia
Fernandez, Natalia Cristina
Pasquini, Juana Maria
author Perez, Maria Julia
author_facet Perez, Maria Julia
Fernandez, Natalia Cristina
Pasquini, Juana Maria
author_role author
author2 Fernandez, Natalia Cristina
Pasquini, Juana Maria
author2_role author
author
dc.subject.none.fl_str_mv Oligodendrocyte
Transferrin
Receptor-Internalization
Signalling
Fyn Tyrosine Kinase
Pi3k/Akt Pathway
Mek/Erk Pathways
Oligodendrocyte Differentiation And Transferrin
topic Oligodendrocyte
Transferrin
Receptor-Internalization
Signalling
Fyn Tyrosine Kinase
Pi3k/Akt Pathway
Mek/Erk Pathways
Oligodendrocyte Differentiation And Transferrin
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Oligodendrocytes are the cells producing the myelin membrane around the axons in the central nervous system and, although apotransferrin (aTf) is required for oligodendrocyte differentiation, the underlying mechanisms are not fully understood. Fyn tyrosine kinase, a member of the Src family of proteins, has been shown to play an important role in myelination by up-regulating the expression of myelin basic protein; however, a molecular link between aTf and Fyn kinase signaling pathway during oligodendrocytes differentiation has not been established yet. Our aim was to investigate whether Fyn kinase, MEK/ERK and PI3K/Akt signaling pathways are required for aTf-stimulation of oligodendrocyte differentiation and also to determine if the transferrin receptor is involved in these mechanisms. Treatment of primary cultures of oligodendroglial precursor cells with aTf leads to Fyn kinase activation by a mechanism that involves transferrin receptor. In turn, Fyn kinase activation promotes MEK-mediated transient phosphorylation of ERK1/2. On the other hand, transferrin receptor internalization also produces rapid and sustained activation of Akt, which involves phosphatidylinositol 3-kinase (PI3K) activation. Finally, aTf incorporated through clathrin-mediated endocytosis increases myelin basic protein, F3-contactin and β-tubulin through Fyn/MEK/ERK pathways, as well as an activation of the PI3K/Akt pathway. Our results also demonstrate that the activation of the pathways necessary for oligodendroglial precursor cell maturation is dependent on AP2 recruitment onto the plasma membrane for clathrin-mediated endocytosis of transferrin receptor.
Fil: Perez, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Quimica Biologica. Cátedra de Química Biológica Patológica; Argentina
Fil: Fernandez, Natalia Cristina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
Fil: Pasquini, Juana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
description Oligodendrocytes are the cells producing the myelin membrane around the axons in the central nervous system and, although apotransferrin (aTf) is required for oligodendrocyte differentiation, the underlying mechanisms are not fully understood. Fyn tyrosine kinase, a member of the Src family of proteins, has been shown to play an important role in myelination by up-regulating the expression of myelin basic protein; however, a molecular link between aTf and Fyn kinase signaling pathway during oligodendrocytes differentiation has not been established yet. Our aim was to investigate whether Fyn kinase, MEK/ERK and PI3K/Akt signaling pathways are required for aTf-stimulation of oligodendrocyte differentiation and also to determine if the transferrin receptor is involved in these mechanisms. Treatment of primary cultures of oligodendroglial precursor cells with aTf leads to Fyn kinase activation by a mechanism that involves transferrin receptor. In turn, Fyn kinase activation promotes MEK-mediated transient phosphorylation of ERK1/2. On the other hand, transferrin receptor internalization also produces rapid and sustained activation of Akt, which involves phosphatidylinositol 3-kinase (PI3K) activation. Finally, aTf incorporated through clathrin-mediated endocytosis increases myelin basic protein, F3-contactin and β-tubulin through Fyn/MEK/ERK pathways, as well as an activation of the PI3K/Akt pathway. Our results also demonstrate that the activation of the pathways necessary for oligodendroglial precursor cell maturation is dependent on AP2 recruitment onto the plasma membrane for clathrin-mediated endocytosis of transferrin receptor.
publishDate 2013
dc.date.none.fl_str_mv 2013-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/1898
Perez, Maria Julia; Fernandez, Natalia Cristina; Pasquini, Juana Maria; Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of action; Elsevier; Experimental Neurology; 248; 10-2013; 262-274
0014-4886
url http://hdl.handle.net/11336/1898
identifier_str_mv Perez, Maria Julia; Fernandez, Natalia Cristina; Pasquini, Juana Maria; Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of action; Elsevier; Experimental Neurology; 248; 10-2013; 262-274
0014-4886
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/reference/url/info:eu-repo/semantics/reference es info:eu-repo/semantics/reference/pmid/23797152
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014488613001878#
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.expneurol.2013.06.014
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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