Brain-Derived Neurotrophic Factor Regulation of Retinal Growth Cone Filopodial Dynamics Is Mediated through Actin Depolymerizing Factor/Cofilin
| Autor: | Alisa E. Shaw, Scott Gehler, James R. Bamburg, Paul C. Letourneau, Patrick D. Sarmiere |
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| Rok vydání: | 2004 |
| Předmět: |
Growth Cones
Development/Plasticity/Repair Motility Chick Embryo macromolecular substances Protein Serine-Threonine Kinases Heterocyclic Compounds 4 or More Rings Retina Tissue Culture Techniques Myosin Animals Pseudopodia Phosphorylation Growth cone Myosin Type II Brain-derived neurotrophic factor rho-Associated Kinases biology Chemistry Brain-Derived Neurotrophic Factor General Neuroscience Microfilament Proteins Intracellular Signaling Peptides and Proteins Cofilin Cell biology Destrin 14-3-3 Proteins Actin Depolymerizing Factors nervous system Actin depolymerizing factor biology.protein Signal Transduction Neurotrophin |
| Zdroj: | The Journal of Neuroscience. 24:10741-10749 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2836-04.2004 |
| Popis: | The molecular mechanisms by which neurotrophins regulate growth cone motility are not well understood. This study investigated the signaling involved in transducing BDNF-induced increases of filopodial dynamics. Our results indicate that BDNF regulates filopodial length and number through a Rho kinase-dependent mechanism. Additionally, actin depolymerizing factor (ADF)/cofilin activity is necessary and sufficient to transduce the effects of BDNF. Our data indicate that activation of ADF/cofilin mimics the effects of BDNF on filopodial dynamics, whereas ADF/cofilin inactivity blocks the effects of BDNF. Furthermore, BDNF promotes the activation of ADF/cofilin by reducing the phosphorylation of ADF/cofilin. Although inhibition of myosin II also enhances filopodial length, our results indicate that BDNF signaling is independent of myosin II activity and that the two pathways result in additive effects on filopodial length. Thus, filopodial extension is regulated by at least two independent mechanisms. The BDNF-dependent pathway works via regulation of ADF/cofilin, independently of myosin II activity. |
| Databáze: | OpenAIRE |
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