Activation of ADF/cofilin mediates attractive growth cone turning toward nerve growth factor and netrin-1
| Autor: | James R. Bamburg, Kevin C. Flynn, Miguel Santiago-Medina, Bonnie M. Marsick, Paul C. Letourneau |
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| Rok vydání: | 2010 |
| Předmět: |
Growth Cones
Chick Embryo macromolecular substances In Vitro Techniques Filamentous actin Amphibian Proteins Article Avian Proteins Xenopus laevis Cellular and Molecular Neuroscience Developmental Neuroscience Cell Movement Ganglia Spinal Nerve Growth Factor Netrin Animals Nerve Growth Factors Phosphorylation Growth cone Cytoskeleton Cells Cultured Neurons Growth cone membrane biology Chemotaxis Tumor Suppressor Proteins Cell Membrane Netrin-1 Cofilin Actins Cell biology Nerve growth factor Actin Depolymerizing Factors Spinal Cord nervous system biology.protein sense organs Protein Multimerization Extracellular Space Retinal Neurons Neurotrophin |
| Zdroj: | Developmental Neurobiology. 70:565-588 |
| ISSN: | 1932-846X 1932-8451 |
| Popis: | Proper neural circuitry requires that growth cones, motile tips of extending axons, respond to molecular guidance cues expressed in the developing organism. However, it is unclear how guidance cues modify the cytoskeleton to guide growth cone pathfinding. Here, we show acute treatment with two attractive guidance cues, nerve growth factor (NGF) and netrin-1, for embryonic dorsal root ganglion and temporal retinal neurons, respectively, results in increased growth cone membrane protrusion, actin polymerization, and filamentous actin (F-actin). ADF/cofilin (AC) family proteins facilitate F-actin dynamics, and we found the inactive phosphorylated form of AC is decreased in NGF- or netrin-1-treated growth cones. Directly increasing AC activity mimics addition of NGF or netrin-1 to increase growth cone protrusion and F-actin levels. Extracellular gradients of NGF, netrin-1, and a cell-permeable AC elicit attractive growth cone turning and increased F-actin barbed ends, F-actin accumulation, and active AC in growth cone regions proximal to the gradient source. Reducing AC activity blunts turning responses to NGF and netrin. Our results suggest that gradients of NGF and netrin-1 locally activate AC to promote actin polymerization and subsequent growth cone turning toward the side containing higher AC activity. |
| Databáze: | OpenAIRE |
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