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PMID: 19208621 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Neuronal Nogo-A modulates growth cone motility via Rho-GTP/LIMK1/cofilin in the unlesioned adult nervous system.

The Journal of biological chemistry ·Vol. 284 ·No. 16 ·2009-04-17 ·Pages 10793-807

Montani L, Gerrits B, Gehrig P, Kempf A, Dimou L, Wollscheid B, Schwab ME

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.

MeSH Terms
Actin Depolymerizing Factors/genetics,metabolism Animals Cells, Cultured Electrophoresis, Gel, Two-Dimensional Growth Cones/metabolism,ultrastructure Isotope Labeling Lim Kinases/genetics,metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Myelin Proteins/genetics,metabolism Neurons/cytology,physiology Nogo Proteins PC12 Cells Protein Array Analysis Rats Retinal Ganglion Cells/cytology,physiology Signal Transduction/physiology Spinal Cord/chemistry,metabolism rho GTP-Binding Proteins/genetics,metabolism
Chemicals
Actin Depolymerizing Factors Myelin Proteins Nogo Proteins Rtn4 protein, mouse Rtn4 protein, rat Lim Kinases Limk1 protein, mouse rho GTP-Binding Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Montani Laura
Brain Research Institute and Functional Genomics Center, University of Zurich, Switzerland.
Gerrits Bertran
Gehrig Peter
Kempf Anissa
Dimou Leda
Wollscheid Bernd
Schwab Martin E
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M808297200
Published
2009-04-17
Epub
2009-00-09
Pages
10793-807
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2667767
Subset
IM
External Links
PubMed source DOI: 10.1074/jbc.M808297200 PMC Full Text View journal details
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