RhoA-kinase and myosin II are required for the maintenance of growth cone polarity and guidance by nerve growth factor
Robert P. Loudon
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129
Search for more papers by this authorLee D. Silver
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129
Search for more papers by this authorHal F. Yee Jr.
Department of Gastroenterology, University of California at San Francisco, San Francisco, California 94143
Search for more papers by this authorCorresponding Author
Gianluca Gallo
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129Search for more papers by this authorRobert P. Loudon
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129
Search for more papers by this authorLee D. Silver
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129
Search for more papers by this authorHal F. Yee Jr.
Department of Gastroenterology, University of California at San Francisco, San Francisco, California 94143
Search for more papers by this authorCorresponding Author
Gianluca Gallo
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129Search for more papers by this authorAbstract
Growth cones are highly polarized and dynamic structures confined to the tips of axons. The polarity of growth cones is in part maintained by suppression of protrusive activity from the distal axon shaft, a process termed axon consolidation. The mechanistic basis of axon consolidation that contributes to the maintenance of growth cone polarity is not clear. We report that inhibition of RhoA-kinase (ROCK) or myosin II resulted in unstable consolidation of the distal axon as evidenced by increased filopodial and lamellipodial extension. Furthermore, when ROCK or myosin II was inhibited lamellipodia formed at the growth cone migrated onto the axon shaft. Analysis of EYFP-actin dynamics in the distal axon revealed that ROCK negatively regulates actin polymerization and initiation of protrusive structures from spontaneously formed axonal F-actin patches, the latter being an effect attributable to ROCK-mediated regulation of myosin II. Inhibition of ROCK or myosin II blocked growth cone turning toward NGF by preventing suppression of protrusive activity away from the source of NGF, resulting in aborted turning responses. These data elucidate the mechanism of growth cone polarity, provide evidence that consolidation of the distal axon is a component of guidance, and identify ROCK as a negative regulator of F-actin polymerization underlying protrusive activity in the distal axon. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006
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