Semaphorin3A regulates axon growth independently of growth cone repulsion via modulation of TrkA signaling
| Autor: | Ayal Ben-Zvi, Zohar Yagil, Omer Lerman, Oded Behar, Liat Ben-Gigi |
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| Rok vydání: | 2007 |
| Předmět: |
Cell signaling
Time Factors Neurite Cell Survival Organogenesis Growth Cones Tropomyosin receptor kinase A Cell Enlargement Transfection Tissue Culture Techniques Mice Ganglia Spinal Nerve Growth Factor medicine Neurites Animals Axon Phosphorylation Receptor trkA Growth cone bcl-2-Associated X Protein Mice Knockout Mice Inbred ICR Chemistry SEMA3A Semaphorin-3A Cell Biology Anatomy Axons Cell biology Enzyme Activation Nerve growth factor medicine.anatomical_structure nervous system Axon guidance Signal Transduction |
| Zdroj: | Cellular signalling. 20(3) |
| ISSN: | 0898-6568 |
| Popis: | Regulation of axon growth is a critical event in neuronal development. Nerve growth factor (NGF) is a strong inducer of axon growth and survival in the dorsal root ganglia (DRG). Paradoxically, high concentrations of NGF are present in the target region where axon growth must slow down for axons to accurately identify their correct targets. Semaphorin3A (Sema3A), a powerful axonal repellent molecule for DRG neurons, is also situated in their target regions. NGF is a modulator of Sema3A-induced repulsion and death. We show that Sema3A is a regulator of NGF-induced neurite outgrowth via the TrkA receptor, independent of its growth cone repulsion activity. First, neurite outgrowth of DRG neurons is more sensitive to Sema3A than repulsion. Second, at concentrations sufficient to significantly inhibit Sema3A-induced repulsion, NGF has no effect on Sema3A-induced axon growth inhibition. Third, Sema3A-induced outgrowth inhibition, but not repulsion activity, is dependent on NGF stimulation. Fourth, Sema3A attenuates TrkA-mediated growth signaling, but not survival signaling, and over-expression of constitutively active TrkA blocks Sema3A-induced axon growth inhibition, suggesting that Sema3A activity is mediated via regulation of NGF/TrkA-induced growth. Finally, quantitative analysis of axon growth in vivo supports the possibility that Sema3A affects axon growth, in addition to its well-documented role in axon guidance. We suggest a model whereby NGF at high concentrations in the target region is important for survival, attraction and inhibition of Sema3A-induced repulsion, while Sema3A inhibits its growth-promoting activity. The combined and cross-modulatory effects of these two signaling molecules ensure the accuracy of the final stages in axon targeting. |
| Databáze: | OpenAIRE |
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