RRC ID 6490
Author Endo M, Ohashi K, Sasaki Y, Goshima Y, Niwa R, Uemura T, Mizuno K.
Title Control of growth cone motility and morphology by LIM kinase and Slingshot via phosphorylation and dephosphorylation of cofilin.
Journal J. Neurosci.
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.
Volume 23(7)
Pages 2527-37
Published 2003-4-1
PII 23/7/2527
PMID 12684437
PMC PMC6742113
MeSH Actin Cytoskeleton / metabolism Actin Depolymerizing Factors Amino Acid Sequence Animals COS Cells Cells, Cultured Chick Embryo Cloning, Molecular Ganglia, Spinal / cytology Ganglia, Spinal / enzymology Growth Cones / enzymology Growth Cones / physiology* Growth Cones / ultrastructure* HeLa Cells Humans Lim Kinases Microfilament Proteins / metabolism* Molecular Sequence Data Movement Neurons / enzymology Phosphoprotein Phosphatases / physiology* Phosphorylation Protein Kinases / analysis Protein Kinases / genetics Protein Kinases / physiology*
IF 5.971
Times Cited 143
Human and Animal Cells