Article

Actin turnover is required to prevent axon retraction driven by endogenous actomyosin contractility

Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
The Journal of Cell Biology (Impact Factor: 9.69). 10/2002; 158(7):1219-28. DOI: 10.1083/jcb.200204140
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ABSTRACT 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, Aug 09, 2015
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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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