Tiam1 as a signaling mediator of nerve growth factor-dependent neurite outgrowth.

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-sp...

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Autores principales:	Shahrzad Shirazi Fard, Julianna Kele, Marçal Vilar, Gustavo Paratcha, Fernanda Ledda
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/db6504eea6b64e5db94498c085c5832e
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spelling	oai:doaj.org-article:db6504eea6b64e5db94498c085c5832e2021-11-25T06:25:19ZTiam1 as a signaling mediator of nerve growth factor-dependent neurite outgrowth.1932-620310.1371/journal.pone.0009647https://doaj.org/article/db6504eea6b64e5db94498c085c5832e2010-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20333299/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Nerve 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.Shahrzad Shirazi FardJulianna KeleMarçal VilarGustavo ParatchaFernanda LeddaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 3, p e9647 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shahrzad Shirazi Fard Julianna Kele Marçal Vilar Gustavo Paratcha Fernanda Ledda Tiam1 as a signaling mediator of nerve growth factor-dependent neurite outgrowth.
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.
format	article
author	Shahrzad Shirazi Fard Julianna Kele Marçal Vilar Gustavo Paratcha Fernanda Ledda
author_facet	Shahrzad Shirazi Fard Julianna Kele Marçal Vilar Gustavo Paratcha Fernanda Ledda
author_sort	Shahrzad Shirazi Fard
title	Tiam1 as a signaling mediator of nerve growth factor-dependent neurite outgrowth.
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.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/db6504eea6b64e5db94498c085c5832e
work_keys_str_mv	AT shahrzadshirazifard tiam1asasignalingmediatorofnervegrowthfactordependentneuriteoutgrowth AT juliannakele tiam1asasignalingmediatorofnervegrowthfactordependentneuriteoutgrowth AT marcalvilar tiam1asasignalingmediatorofnervegrowthfactordependentneuriteoutgrowth AT gustavoparatcha tiam1asasignalingmediatorofnervegrowthfactordependentneuriteoutgrowth AT fernandaledda tiam1asasignalingmediatorofnervegrowthfactordependentneuriteoutgrowth
_version_	1718413773906116608

Tiam1 as a signaling mediator of nerve growth factor-dependent neurite outgrowth.

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