Actin Turnover Is Required to Prevent Axon Retraction Driven by Endogenous Actomyosin Contractility

• Published in: The Journal of cell biology Vol. 158; no. 7; pp. 1219 - 1228
• Main Authors: Gallo, Gianluca, Yee, Hal F., Letourneau, Paul C.
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 30.09.2002; The Rockefeller University Press
• Subjects: Actin Cytoskeleton - drug effects; Actin Cytoskeleton - metabolism; Actins; Actins - metabolism; Actomyosin - metabolism; Actomyosin - pharmacology; Animals; Antibodies; Antineoplastic Agents - pharmacology; Axons; Axons - drug effects; Axons - physiology; Cells, Cultured; Cellular biology; Chick Embryo - cytology; Chick Embryo - drug effects; Chick Embryo - metabolism; Depolymerization; Depsipeptides; Ephrin-A2 - pharmacology; Fibroblasts; Ganglia, Spinal - cytology; Ganglia, Spinal - drug effects; Ganglia, Spinal - metabolism; Growth cones; Growth Cones - drug effects; Growth Cones - metabolism; Immunoenzyme Techniques; Intracellular Signaling Peptides and Proteins; Microinjections; Microscopy, Video; Microtubules; Microtubules - drug effects; Microtubules - metabolism; Myosin-Light-Chain Kinase - antagonists & inhibitors; Neurons; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Peptides; Peptides, Cyclic - pharmacology; Phalloidine - pharmacology; Phosphorylation; Physiological regulation; Protein Binding - drug effects; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Proteins; Retina - cytology; Retina - drug effects; Retina - metabolism; rho-Associated Kinases; rhoA GTP-Binding Protein - metabolism
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200204140

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.