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XB-ART-42130
Dev Neurobiol July 1, 2010; 70 (8): 565-88.

Activation of ADF/cofilin mediates attractive growth cone turning toward nerve growth factor and netrin-1.

Marsick BM , Flynn KC , Santiago-Medina M , Bamburg JR , Letourneau PC .


Abstract
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.

PubMed ID: 20506164
PMC ID: PMC2908028
Article link: Dev Neurobiol
Grant support: [+]
Genes referenced: actl6a dstn ngf ntn1

References [+] :
Andrianantoandro, Mechanism of actin filament turnover by severing and nucleation at different concentrations of ADF/cofilin. 2006, Pubmed


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