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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/67622
Ver los metadatos del registro completo
id |
CONICETDig_9cdb82b61f1302cde9db953becc262dc |
---|---|
oai_identifier_str |
oai:ri.conicet.gov.ar:11336/67622 |
network_acronym_str |
CONICETDig |
repository_id_str |
3498 |
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) |
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 |
_version_ |
1842269948276113408 |
score |
13.13397 |