Abstract
Semaphorin 3A is a chemorepulsive axonal guidance molecule that depolymerizes the actin cytoskeleton and collapses growth cones of dorsal root ganglia neurons. Here we investigate the role of LIM-kinase 1, which phosphorylates an actin-depolymerizing protein, cofilin, in semaphorin 3A-induced growth cone collapse. Semaphorin 3A induced phosphorylation and dephosphorylation of cofilin at growth cones sequentially. A synthetic cell-permeable peptide containing a cofilin phosphorylation site inhibited LIM-kinase in vitro and in vivo, and essentially suppressed semaphorin 3A-induced growth cone collapse. A dominant-negative LIM kinase, which could not be activated by PAK or ROCK, suppressed the collapsing activity of semaphorin 3A. Phosphorylation of cofilin by LIM-kinase may be a critical signaling event in growth cone collapse by semaphorin 3A.
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Acknowledgements
We thank S. Ohno (Yokohama City University School of Medicine, Japan), T.C. Saido (Riken, Japan), and members of the Yahara lab and Sehara-Fujisawa lab for their comments and suggestions. We thank H. Fujisawa (Nagoya University, Japan) and T. Nagase (Kazusa DNA Research Institute, Japan) for murine neuropilin-1 and human plexin-A2 cDNAs, respectively. We also thank A. Ghosh at Johns Hopkins University Medical School for critical reading of our manuscript.
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Aizawa, H., Wakatsuki, S., Ishii, A. et al. Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse. Nat Neurosci 4, 367–373 (2001). https://doi.org/10.1038/86011
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DOI: https://doi.org/10.1038/86011
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