Fig. 6. Model of the proposed role of RhoA-kinase (ROCK) in the coordinated regulation of the axonal F-actin cytoskeleton and myosin II activity in response to semaphorin 3A signaling. (A) Under normal conditions, RhoA-kinase (ROCK) activity is low. However, as previously reported (Loudon et al., 2006), endogenous baseline-ROCK-activity contributes to the negative regulation of protrusion, and promotes myosin II activity and the formation of a population of F-actin bundles in growth cones. (B) Following activation of RhoA by semaphorin 3A, ROCK activity is elevated, resulting in the suppression of protrusive activity, which contributes to growth cone collapse. In concert, elevated ROCK activity promotes the activation of myosin II and the formation of non-protrusive intra-axonal F-actin bundles that serve as a substratum for myosin II to generate the contractile forces required to drive axon retraction. Since inhibition of ROCK only partially blocked the formation of axonal bundles, additional pathways not elucidated in this report probably contribute to bundle formation. This diagram shows the proposed map of ROCK-myosin-II functions in growth cone collapse and axon retraction induced by semaphorin 3A. Since growth cone collapse occurs before axon retraction, the time course of the functions of ROCK-myosin-II in these two processes is not directly shown here.