The N-terminal domain of Nogo-A inhibits cell adhesion and axonal outgrowth by an integrin-specific mechanism.

Myelin-derived Nogo-A protein limits axonal growth after CNS injury. One domain binds to the Nogo-66 receptor to inhibit axonal outgrowth, whereas a second domain, Amino-Nogo, inhibits axonal outgrowth and cell adhesion through unknown mechanisms. Here, we show that Amino-Nogo inhibition depends strictly on the composition of the extracellular matrix, suggesting ...
that Amino-Nogo inhibits the function of certain integrins. Amino-Nogo inhibition can be partially overcome by antibodies that activate integrin beta1 or by the addition of Mn2+, an integrin activator. Furthermore, Amino-Nogo reduces focal adhesion kinase activation by fibronectin. Analysis of various cell lines reveals that alpha(v)beta3, alpha5, and alpha4 integrins are sensitive to Amino-Nogo, but alpha6 integrin is not. Both alpha(v) and alpha5 integrins have widespread expression in adult brain and are found in axonal growth cones. Thus, inhibition of integrin signaling by Amino-Nogo contributes to the failure of CNS axon regeneration.
Mesh Terms:
Animals, Axons, CHO Cells, COS Cells, Cell Adhesion, Chick Embryo, Chlorocebus aethiops, Cricetinae, Cricetulus, Growth Inhibitors, Humans, Integrins, Jurkat Cells, Mice, Myelin Proteins, Nerve Regeneration, Nogo Proteins, Peptide Fragments, Protein Structure, Tertiary, Rats
J Neurosci
Date: Jan. 30, 2008
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