XB-ART-42130
Dev Neurobiol
2010 Jul 01;708:565-88. doi: 10.1002/dneu.20800.
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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
.
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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.
???displayArticle.pubmedLink??? 20506164
???displayArticle.pmcLink??? PMC2908028
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???displayArticle.grants??? [+]
EY07133 NEI NIH HHS , HD019950 NICHD NIH HHS , NS40371 NINDS NIH HHS , NS41564 NINDS NIH HHS , NS48660 NINDS NIH HHS , R01 HD019950-22 NICHD NIH HHS , R01 HD019950-23 NICHD NIH HHS , R01 NS041564-11 NINDS NIH HHS , R01 HD019950 NICHD NIH HHS , R01 NS041564 NINDS NIH HHS , R01 NS040371 NINDS NIH HHS , R56 NS041564 NINDS NIH HHS , T32 EY007133 NEI NIH HHS , F31 NS048660 NINDS NIH HHS
Species referenced: Xenopus laevis
Genes referenced: actl6a dstn ngf ntn1
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