Actin turnover is required to prevent axon retraction by endogenous actomyosin activity

Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
The Journal of Cell Biology (Impact Factor: 9.83). 10/2002; 158(7):1219-28. DOI: 10.1083/jcb.200204140
Source: PubMed


Growth cone motility and guidance depend on the dynamic reorganization of filamentous actin (F-actin). In the growth cone, F-actin undergoes turnover, which is the exchange of actin subunits from existing filaments. However, the function of F-actin turnover is not clear. We used jasplakinolide (jasp), a cell-permeable macrocyclic peptide that inhibits F-actin turnover, to study the role of F-actin turnover in axon extension. Treatment with jasp caused axon retraction, demonstrating that axon extension requires F-actin turnover. The retraction of axons in response to the inhibition of F-actin turnover was dependent on myosin activity and regulated by RhoA and myosin light chain kinase. Significantly, the endogenous myosin-based contractility was sufficient to cause axon retraction, because jasp did not alter myosin activity. Based on these observations, we asked whether guidance cues that cause axon retraction (ephrin-A2) inhibit F-actin turnover. Axon retraction in response to ephrin-A2 correlated with decreased F-actin turnover and required RhoA activity. These observations demonstrate that axon extension depends on an interaction between endogenous myosin-driven contractility and F-actin turnover, and that guidance cues that cause axon retraction inhibit F-actin turnover.

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Available from: Gianluca Gallo, Sep 29, 2015
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    • "This assembled F-actin undergoes retrograde actin flow and depolymerization at the pointed end near the actin arc [2]–[5]. These processes are equally important in the modulation of growth cone behavior [6]. "
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    • "Although ephrin-A2 treatment reduces total F-actin in growth cones, the F-actin reduction is greater in the P-domain that in the growth cone center. F-actin bundles persist in the C-domain of ephrin-A2 treated growth cones (Fig. 2) [Roche et al., 2009], and as we previously reported, these bundles are more stable than F-actin arrays in control growth cones [Gallo et al., 2002]. Changes in the location and activities of several actin regulatory proteins coordinate this actin filament reorganization [Gallo, 2006; Brown and Bridgman, 2009]. "
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