Control of growth cone motility and morphology by LIM kinase and slingshot via phosphorylation and dephosphorylation of cofilin

Mitsuharu Endo, Kazumasa Ohashi, Yukio Sasaki, Yoshio Goshima, Ryusuke Niwa, Tadashi Uemura, Kensaku Mizuno

Research output: Contribution to journalArticlepeer-review

185 Citations (Scopus)

Abstract

Growth cone motility and morphology are based on actin-filament dynamics. Cofilin plays an essential role for the rapid turnover of actin filaments by severing and depolymerizing them. The activity of cofilin is repressed by phosphorylation at Ser3 by LIM kinase (LIMK, in which LIM is an acronym of the three gene products Lin-11, Isl-1, and Mec-3) and is reactivated by dephosphorylation by phosphatases, termed Slingshot (SSH). We investigated the roles of cofilin, LIMK, and SSH in the growth cone motility and morphology and neurite extension by expressing fluorescence protein-labeled cofilin, LIMK1, SSH1, or their mutants in chick dorsal root ganglion (DRG) neurons and then monitoring live images of growth cones by time-lapse video fluorescence microscopy. The expression of LIMK1 remarkably repressed growth cone motility and neurite extension, whereas the expression of SSH1 or a nonphosphorylatable S3A mutant of cofilin enhanced these events. The fan-like shape of growth cones was disorganized by the expression of any of these proteins. The repressive effects on growth cone behavior by LIMK1 expression were significantly rescued by the coexpression of S3A-cofilin or SSH1. These findings suggest that LIMK1 and SSH1 play critical roles in controlling growth cone motility and morphology and neurite extension by regulating the activity of cofilin and may be involved in signaling pathways that regulate stimulus-induced growth cone guidance. Using various mutants of cofilin, we also obtained evidence that the actin-filament-severing activity of cofilin is critical for growth cone motility and neurite extension.

Original languageEnglish
Pages (from-to)2527-2537
Number of pages11
JournalJournal of Neuroscience
Volume23
Issue number7
DOIs
Publication statusPublished - 2003 Apr 1

Keywords

  • Actin-depolymerizing factor
  • Cofilin
  • Growth cone guidance
  • LIM kinase
  • Neurite outgrowth
  • Slingshot

ASJC Scopus subject areas

  • Neuroscience(all)

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