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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Bibliographic Details
Published in:PloS one 2010-03, Vol.5 (3), p.e9647-e9647
Main Authors: Shirazi Fard, Shahrzad, Kele, Julianna, Vilar, Marçal, Paratcha, Gustavo, Ledda, Fernanda
Format: Article
Language:English
Subjects:
Activation
Animals
Axonogenesis
Biochemistry
Cell adhesion & migration
Cell Biology/Cell Signaling
Cell Biology/Neuronal Signaling Mechanisms
Cell Differentiation
Cellular biology
Cercopithecus aethiops
COS Cells
Cytoskeleton
Elongation
G proteins
Growth factors
Guanine
Guanine Nucleotide Exchange Factors - metabolism
Guanosine triphosphate
Humans
Intellectual disabilities
Kinases
Laboratories
Medicin och hälsovetenskap
Molecular modelling
Morphogenesis
Neoplasm Proteins - metabolism
Nerve growth factor
Nerve Growth Factor - metabolism
Neurites - metabolism
Neurons
Neurons - metabolism
Neuroscience/Neuronal Signaling Mechanisms
Neurosciences
PC12 Cells
Phosphorylation
Physiological aspects
Proteins
rac1 GTP-Binding Protein - metabolism
Rac1 protein
ras Proteins - metabolism
Rats
Receptor, trkA - metabolism
Signal Transduction
Signaling
T-Lymphoma Invasion and Metastasis-inducing Protein 1
Tiam1 protein
Trends
TrkA protein
TrkA receptors
Tyrosine
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0009647