Tiam1 as a signaling mediator of Nerve Growth Factor-dependent neurite outgrowth

Autores
Shirazi Fard, Shahrzad; Kele, Julianna; Vilar, Marçal; Paratcha, Gustavo; Ledda, Maria Fernanda
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Nerve Growth Factor (NGF)-induced neuronal differentiation requires the activation of members of the Rho family of small GTPases. However, the molecular mechanisms through which NGF regulates cytoskeletal changes and neurite outgrowth are not totally understood. In this work, we identify the Rac1-specific guanine exchange factor (GEF) Tiam1 as a novel mediator of NGF/TrkA-dependent neurite elongation. In particular, we report that knockdown of Tiam1 causes a significant reduction in Rac1 activity and neurite outgrowth induced by NGF. Physical interaction between Tiam1 and active Ras (Ras- GTP), but not tyrosine phosphorylation of Tiam1, plays a central role in Rac1 activation by NGF. In addition, our findings indicate that Ras is required to associate Tiam1 with Rac1 and promote Rac1 activation upon NGF stimulation. Taken together, these findings define a novel molecular mechanism through which Tiam1 mediates TrkA signaling and neurite outgrowth induced by NGF.
Fil: Shirazi Fard, Shahrzad. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Kele, Julianna. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Vilar, Marçal. Universidad de Valencia; España
Fil: Paratcha, Gustavo. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Ledda, Maria Fernanda. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Materia
NGF
Tiam1
Neuronal differentiation
Rac1 GTPase
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:11336/67622

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network_name_str CONICET Digital (CONICET)
spelling Tiam1 as a signaling mediator of Nerve Growth Factor-dependent neurite outgrowthShirazi Fard, ShahrzadKele, JuliannaVilar, MarçalParatcha, GustavoLedda, Maria FernandaNGFTiam1Neuronal differentiationRac1 GTPasehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Nerve Growth Factor (NGF)-induced neuronal differentiation requires the activation of members of the Rho family of small GTPases. However, the molecular mechanisms through which NGF regulates cytoskeletal changes and neurite outgrowth are not totally understood. In this work, we identify the Rac1-specific guanine exchange factor (GEF) Tiam1 as a novel mediator of NGF/TrkA-dependent neurite elongation. In particular, we report that knockdown of Tiam1 causes a significant reduction in Rac1 activity and neurite outgrowth induced by NGF. Physical interaction between Tiam1 and active Ras (Ras- GTP), but not tyrosine phosphorylation of Tiam1, plays a central role in Rac1 activation by NGF. In addition, our findings indicate that Ras is required to associate Tiam1 with Rac1 and promote Rac1 activation upon NGF stimulation. Taken together, these findings define a novel molecular mechanism through which Tiam1 mediates TrkA signaling and neurite outgrowth induced by NGF.Fil: Shirazi Fard, Shahrzad. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Kele, Julianna. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Vilar, Marçal. Universidad de Valencia; EspañaFil: Paratcha, Gustavo. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ledda, Maria Fernanda. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaPublic Library of Science2010-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/67622Shirazi Fard, Shahrzad; Kele, Julianna; Vilar, Marçal; Paratcha, Gustavo; Ledda, Maria Fernanda; Tiam1 as a signaling mediator of Nerve Growth Factor-dependent neurite outgrowth; Public Library of Science; Plos One; 5; 3; 3-2010; 1-11; e96471932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0009647info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0009647info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:06:14Zoai:ri.conicet.gov.ar:11336/67622instacron: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:34982025-09-03 10:06:14.538CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Tiam1 as a signaling mediator of Nerve Growth Factor-dependent neurite outgrowth
title Tiam1 as a signaling mediator of Nerve Growth Factor-dependent neurite outgrowth
spellingShingle Tiam1 as a signaling mediator of Nerve Growth Factor-dependent neurite outgrowth
Shirazi Fard, Shahrzad
NGF
Tiam1
Neuronal differentiation
Rac1 GTPase
title_short Tiam1 as a signaling mediator of Nerve Growth Factor-dependent neurite outgrowth
title_full Tiam1 as a signaling mediator of Nerve Growth Factor-dependent neurite outgrowth
title_fullStr Tiam1 as a signaling mediator of Nerve Growth Factor-dependent neurite outgrowth
title_full_unstemmed Tiam1 as a signaling mediator of Nerve Growth Factor-dependent neurite outgrowth
title_sort Tiam1 as a signaling mediator of Nerve Growth Factor-dependent neurite outgrowth
dc.creator.none.fl_str_mv Shirazi Fard, Shahrzad
Kele, Julianna
Vilar, Marçal
Paratcha, Gustavo
Ledda, Maria Fernanda
author Shirazi Fard, Shahrzad
author_facet Shirazi Fard, Shahrzad
Kele, Julianna
Vilar, Marçal
Paratcha, Gustavo
Ledda, Maria Fernanda
author_role author
author2 Kele, Julianna
Vilar, Marçal
Paratcha, Gustavo
Ledda, Maria Fernanda
author2_role author
author
author
author
dc.subject.none.fl_str_mv NGF
Tiam1
Neuronal differentiation
Rac1 GTPase
topic NGF
Tiam1
Neuronal differentiation
Rac1 GTPase
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Nerve Growth Factor (NGF)-induced neuronal differentiation requires the activation of members of the Rho family of small GTPases. However, the molecular mechanisms through which NGF regulates cytoskeletal changes and neurite outgrowth are not totally understood. In this work, we identify the Rac1-specific guanine exchange factor (GEF) Tiam1 as a novel mediator of NGF/TrkA-dependent neurite elongation. In particular, we report that knockdown of Tiam1 causes a significant reduction in Rac1 activity and neurite outgrowth induced by NGF. Physical interaction between Tiam1 and active Ras (Ras- GTP), but not tyrosine phosphorylation of Tiam1, plays a central role in Rac1 activation by NGF. In addition, our findings indicate that Ras is required to associate Tiam1 with Rac1 and promote Rac1 activation upon NGF stimulation. Taken together, these findings define a novel molecular mechanism through which Tiam1 mediates TrkA signaling and neurite outgrowth induced by NGF.
Fil: Shirazi Fard, Shahrzad. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Kele, Julianna. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Vilar, Marçal. Universidad de Valencia; España
Fil: Paratcha, Gustavo. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Ledda, Maria Fernanda. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
description Nerve Growth Factor (NGF)-induced neuronal differentiation requires the activation of members of the Rho family of small GTPases. However, the molecular mechanisms through which NGF regulates cytoskeletal changes and neurite outgrowth are not totally understood. In this work, we identify the Rac1-specific guanine exchange factor (GEF) Tiam1 as a novel mediator of NGF/TrkA-dependent neurite elongation. In particular, we report that knockdown of Tiam1 causes a significant reduction in Rac1 activity and neurite outgrowth induced by NGF. Physical interaction between Tiam1 and active Ras (Ras- GTP), but not tyrosine phosphorylation of Tiam1, plays a central role in Rac1 activation by NGF. In addition, our findings indicate that Ras is required to associate Tiam1 with Rac1 and promote Rac1 activation upon NGF stimulation. Taken together, these findings define a novel molecular mechanism through which Tiam1 mediates TrkA signaling and neurite outgrowth induced by NGF.
publishDate 2010
dc.date.none.fl_str_mv 2010-03
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/11336/67622
Shirazi Fard, Shahrzad; Kele, Julianna; Vilar, Marçal; Paratcha, Gustavo; Ledda, Maria Fernanda; Tiam1 as a signaling mediator of Nerve Growth Factor-dependent neurite outgrowth; Public Library of Science; Plos One; 5; 3; 3-2010; 1-11; e9647
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/67622
identifier_str_mv Shirazi Fard, Shahrzad; Kele, Julianna; Vilar, Marçal; Paratcha, Gustavo; Ledda, Maria Fernanda; Tiam1 as a signaling mediator of Nerve Growth Factor-dependent neurite outgrowth; Public Library of Science; Plos One; 5; 3; 3-2010; 1-11; e9647
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0009647
info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0009647
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
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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)
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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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