Open AccessRhoA‐kinase and myosin II are required for the maintenance of growth cone polarity and guidance by nerve growth factor
Author(s) -
Loudon Robert P.,
Silver Lee D.,
Yee Hal F.,
Gallo Gianluca
Publication year - 2006
Publication title -
journal of neurobiology
Language(s) - English
Resource type - Journals
eISSN - 1097-4695
pISSN - 0022-3034
DOI - 10.1002/neu.20258
Subject(s) - growth cone , axon , rhoa , biology , lamellipodium , microbiology and biotechnology , actin , polarity (international relations) , myosin , axon guidance , rho associated protein kinase , myosin light chain kinase , neuroscience , biophysics , anatomy , kinase , signal transduction , cytoskeleton , biochemistry , cell
Abstract 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