Src and FAK are key early signalling intermediates required for neurite growth in NGF-responsive adult DRG neurons

Tucker, Budd A.; Rahimtula, Masuma; Mearow, Karen M.

doi:10.1016/j.cellsig.2007.10.014

Cited by 67 publications

(63 citation statements)

References 47 publications

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“…Generally, integrin signalling involves complex actions of several adhesion molecules. Among these, FAK has been considered to be one of the most important neurite outgrowth regulation factors in neuron cells [18,49]. Our study also demonstrated that MSCs conditioned with FAK knockdown did not show neuronal outgrowth, suggesting that FAK is a key dominant protein in the intracellular signalling pathway to neuronal differentiation of MSCs within the collagen three-dimensional matrix.…”

Section: Discussionsupporting

confidence: 64%

Collagen gel three-dimensional matrices combined with adhesive proteins stimulate neuronal differentiation of mesenchymal stem cells

Lee

et al. 2011

J. R. Soc. Interface.

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Three-dimensional gel matrices provide specialized microenvironments that mimic native tissues and enable stem cells to grow and differentiate into specific cell types. Here, we show that collagen three-dimensional gel matrices prepared in combination with adhesive proteins, such as fibronectin (FN) and laminin (LN), provide significant cues to the differentiation into neuronal lineage of mesenchymal stem cells (MSCs) derived from rat bone marrow. When cultured within either a three-dimensional collagen gel alone or one containing either FN or LN, and free of nerve growth factor (NGF), the MSCs showed the development of numerous neurite outgrowths. These were, however, not readily observed in two-dimensional culture without the use of NGF. Immunofluorescence staining, western blot and fluorescence-activated cell sorting analyses demonstrated that a large population of cells was positive for NeuN and glial fibrillary acidic protein, which are specific to neuronal cells, when cultured in the three-dimensional collagen gel. The dependence of the neuronal differentiation of MSCs on the adhesive proteins containing three-dimensional gel matrices is considered to be closely related to focal adhesion kinase (FAK) activation through integrin receptor binding, as revealed by an experiment showing no neuronal outgrowth in the FAK-knockdown cells and stimulation of integrin b1 gene. The results provided herein suggest the potential role of three-dimensional collagen-based gel matrices combined with adhesive proteins in the neuronal differentiation of MSCs, even without the use of chemical differentiation factors. Furthermore, these findings suggest that three-dimensional gel matrices might be useful as nerve-regenerative scaffolds.

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Section: Discussionsupporting

confidence: 64%

Collagen gel three-dimensional matrices combined with adhesive proteins stimulate neuronal differentiation of mesenchymal stem cells

Lee

et al. 2011

J. R. Soc. Interface.

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“…Since laminin-1 self-assembly has been reported (Yurchenco et al, 1992), local laminin-1 aggregation might strengthen in focal GM1 aggregation structures in lipid rafts. Laminin-1-NGF-mediated neurite outgrowth requires the activation of the Src family of tyrosine kinases (SFK), which results in the activation of downstream signaling intermediates, such as FAK and Akt (Tucker et al, 2008). We also demonstrated in this study that laminin-1 and NGF activate Akt and MAPK (supplementary material Fig.…”

Section: Discussionmentioning

confidence: 60%

Binding of laminin-1 to monosialoganglioside GM1 in lipid rafts is crucial for neurite outgrowth

Ichikawa

Iwabuchi

Kurihara

et al. 2009

Journal of Cell Science

109

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where TrkA colocalizes with β1 integrin -and the activation of Lyn, Akt and MAPK to promote the outgrowth of neurites. Our results suggest that the binding of laminin-1 to GM1 facilitates the formation of a focal microdomain in the membrane, and enhances signal transduction that promotes neurite outgrowth by linking NGF-TrkA signaling with the laminin-integrin signaling pathways. Supplementary material available online at

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“…It has been shown that neuronal stimulation with NGF results in rapid and specific activation of both the FAK and the MAPK signaling pathways and that inhibition of FAK activity in this con- S cores (mean 8 SD) as evaluated by Irwin [35]: higher score presents more (better, higher) activity (performance, response) or parameters are scored as present (1) or absent (0). text attenuates both NGF-induced PI3-K/Akt and MEK/ MAPK signaling pathways, as well as neurite growth [42] . Previous reports indicate that FAK is an important modulator of the NGF signaling pathway, suggesting the possibility that FAK might interfere with the regulation of TrkA receptor levels induced by NGF [43] .…”

Section: Fak and Hippocampal Neuronal Outgrowthmentioning

confidence: 99%

Focal Adhesion Kinase Regulates Neuronal Growth, Synaptic Plasticity and Hippocampus-Dependent Spatial Learning and Memory

Monje¹,

Kim

Pollak³

et al. 2011

Neurosignals

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The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase abundantly expressed in the mammalian brain and highly enriched in neuronal growth cones. Inhibitory and facilitatory activities of FAK on neuronal growth have been reported and its role in neuritic outgrowth remains controversial. Unlike other tyrosine kinases, such as the neurotrophin receptors regulating neuronal growth and plasticity, the relevance of FAK for learning and memory in vivo has not been clearly defined yet. A comprehensive study aimed at determining the role of FAK in neuronal growth, neurotransmitter release and synaptic plasticity in hippocampal neurons and in hippocampus-dependent learning and memory was therefore undertaken using the mouse model. Gain- and loss-of-function experiments indicated that FAK is a critical regulator of hippocampal cell morphology. FAK mediated neurotrophin-induced neuritic outgrowth and FAK inhibition affected both miniature excitatory postsynaptic potentials and activity-dependent hippocampal long-term potentiation prompting us to explore the possible role of FAK in spatial learning and memory in vivo. Our data indicate that FAK has a growth-promoting effect, is importantly involved in the regulation of the synaptic function and mediates in vivo hippocampus-dependent spatial learning and memory.

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Src and FAK are key early signalling intermediates required for neurite growth in NGF-responsive adult DRG neurons

Cited by 67 publications

References 47 publications

Collagen gel three-dimensional matrices combined with adhesive proteins stimulate neuronal differentiation of mesenchymal stem cells

Collagen gel three-dimensional matrices combined with adhesive proteins stimulate neuronal differentiation of mesenchymal stem cells

Binding of laminin-1 to monosialoganglioside GM1 in lipid rafts is crucial for neurite outgrowth

Focal Adhesion Kinase Regulates Neuronal Growth, Synaptic Plasticity and Hippocampus-Dependent Spatial Learning and Memory

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