Neuronal Nogo-A modulates growth cone motility via Rho-GTP/LIMK1/cofilin in the unlesioned adult nervous system.
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.
Montani
Laura
L
Brain Research Institute and Functional Genomics Center, University of Zurich, Switzerland.
Gerrits
Bertran
B
Gehrig
Peter
P
Kempf
Anissa
A
Dimou
Leda
L
Wollscheid
Bernd
B
Schwab
Martin E
ME
D051339:Actin Depolymerizing Factors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D015180:Electrophoresis, Gel, Two-Dimensional; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D007553:Isotope Labeling; D054461:Lim Kinases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D000070798:Nogo Proteins; D016716:PC12 Cells; D040081:Protein Array Analysis; D051381:Rats; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000737:chemistry / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D051339:Actin Depolymerizing Factors; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat; D054461:Lim Kinases; C515893:Limk1 protein, mouse; D020741:rho GTP-Binding Proteins