RRC ID 70024
Author Montani L, Gerrits B, Gehrig P, Kempf A, Dimou L, Wollscheid B, Schwab ME.
Title Neuronal Nogo-A modulates growth cone motility via Rho-GTP/LIMK1/cofilin in the unlesioned adult nervous system.
Journal J Biol Chem
Abstract Nogo-A has been extensively studied as a myelin-associated neurite outgrowth inhibitor in the lesioned adult central nervous system. However, its role in the intact central nervous system has not yet been clarified. Analysis of the intact adult nervous system of C57BL/6 Nogo-A knock-out (KO) versus wild-type (WT) mice by a combined two-dimensional gel electrophoresis and isotope-coded affinity tagging approach revealed regulation of cytoskeleton-, transport-, and signaling growth-related proteins, pointing to regulation of the actin cytoskeleton, the neuronal growth machinery, and in particular the Rho-GTPase/LIMK1/cofilin pathway. Nogo-A KO adult neurons showed enlarged, more motile growth cones compared with WT neurons. The phenotype was reproduced by acute in vitro neutralization of neuronal Nogo-A. LIMK1 phosphorylation was increased in Nogo-A KO growth cones, and its reduction caused the decrease of KO growth cone motility to WT levels. Our study suggests that in the unlesioned adult nervous system, neuronal Nogo-A can restrict neuronal growth through negative modulation of growth cone motility.
Volume 284(16)
Pages 10793-807
Published 2009-4-17
DOI 10.1074/jbc.M808297200
PII S0021-9258(20)39922-1
PMID 19208621
PMC PMC2667767
MeSH Actin Depolymerizing Factors / genetics Actin Depolymerizing Factors / metabolism* Animals Cells, Cultured Electrophoresis, Gel, Two-Dimensional Growth Cones / metabolism* Growth Cones / ultrastructure Isotope Labeling Lim Kinases / genetics Lim Kinases / metabolism* Male Mice Mice, Inbred C57BL Mice, Knockout Myelin Proteins / genetics Myelin Proteins / metabolism* Neurons / cytology Neurons / physiology* Nogo Proteins PC12 Cells Protein Array Analysis Rats Retinal Ganglion Cells / cytology Retinal Ganglion Cells / physiology Signal Transduction / physiology Spinal Cord / chemistry Spinal Cord / metabolism rho GTP-Binding Proteins / genetics rho GTP-Binding Proteins / metabolism*
IF 4.238
Human and Animal Cells Jyg-MC(B)(RCB0527)