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Published online 28 May 2001. doi:10.1083/jcb.153.5.1071
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© The Rockefeller University Press, 0021-9525/2001//1071 $5.00
The Journal of Cell Biology, Volume 153, Number 5, , 2001 1071-1084

Original Article

Growth Cone Collapse through Coincident Loss of Actin Bundles and Leading Edge Actin without Actin Depolymerization



Feng-quan Zhoua and Christopher S. Cohana

a Department of Anatomy and Cell Biology, State University of New York at Buffalo, Buffalo, New York 14214
Dept. of Anatomy and Cell Biology, State University of New York at Buffalo, Buffalo, NY 14214.(716) 829-2915(716) 829-3081

ccohan{at}buffalo.edu

Repulsive guidance cues can either collapse the whole growth cone to arrest neurite outgrowth or cause asymmetric collapse leading to growth cone turning. How signals from repulsive cues are translated by growth cones into this morphological change through rearranging the cytoskeleton is unclear. We examined three factors that are able to induce the collapse of extending Helisoma growth cones in conditioned medium, including serotonin, myosin light chain kinase inhibitor, and phorbol ester. To study the cytoskeletal events contributing to collapse, we cultured Helisoma growth cones on polylysine in which lamellipodial collapse was prevented by substrate adhesion. We found that all three factors that induced collapse of extending growth cones also caused actin bundle loss in polylysine-attached growth cones without loss of actin meshwork. In addition, actin bundle loss correlated with specific filamentous actin redistribution away from the leading edge that is characteristic of repulsive factors. Finally, we provide direct evidence using time-lapse studies of extending growth cones that actin bundle loss paralleled collapse. Taken together, these results suggest that actin bundles could be a common cytoskeletal target of various collapsing factors, which may use different signaling pathways that converge to induce growth cone collapse.

Key Words: growth cone • collapse • actin filaments • actin bundles • axon guidance

© 2001 The Rockefeller University Press

Abbreviations used in this paper: BDM, 2,3-butanedione monoxime; BIS, bisindolylmaleimide I; C-domain, central domain; CM, conditioned medium; DM, defined medium; ERM, ezrin/radixin/moesin; LPA, lysophosphatidic acid; MLCK, myosin light chain kinase; ML-7, 1-(5-Iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine-HCl; PA, polylysine attached; P-domain, peripheral domain; STS, staurosporine; TPA, phorbol-12 myristate 13-acetate; WT, wortmannin.


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