2 research outputs found
Neuronal Nogo-A Modulates Growth Cone Motility via Rho-GTP/LIMK1/Cofilin in the Unlesioned Adult Nervous System*Sâ
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