Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse

Hiroyuki Aizawa, Shuji Wakatsuki, Ai Ishii, Kenji Moriyama, Yukio Sasaki, Kazumasa Ohashi, Yoko Sekine-Aizawa, Atsuko Sehara-Fujisawa, Kensaku Mizuno, Yoshio Goshima, Ichiro Yahara

Research output: Contribution to journalArticlepeer-review

285 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)367-373
Number of pages7
JournalNature Neuroscience
Volume4
Issue number4
DOIs
Publication statusPublished - 2001 Apr 12

ASJC Scopus subject areas

  • Neuroscience(all)

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