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The Journal of Neuroscience, January 30, 2008, 28(5):1262-1269; doi:10.1523/JNEUROSCI.1068-07.2008

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 Previous Article

Development/Plasticity/Repair
The N-Terminal Domain of Nogo-A Inhibits Cell Adhesion and Axonal Outgrowth by an Integrin-Specific Mechanism

Fenghua Hu^1,2 and Stephen M. Strittmatter^1,2

¹Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510, and ²Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520

Correspondence should be addressed to Stephen M. Strittmatter, Department of Neurology, Yale University School of Medicine, New Haven, CT 06520. Email: stephen.strittmatter{at}yale.edu

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 β1 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 vβ3, 5, and 4 integrins are sensitive to Amino-Nogo, but 6 integrin is not. Both v and 5 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.

Key words: myelin; axon regeneration; spinal cord injury; outgrowth inhibitor; cell adhesion; integrin

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Received March 8, 2007; revised Nov. 16, 2007; accepted Dec. 19, 2007.

Correspondence should be addressed to Stephen M. Strittmatter, Department of Neurology, Yale University School of Medicine, New Haven, CT 06520. Email: stephen.strittmatter{at}yale.edu

This article has been cited by other articles:

				M. R. Andrews, S. Czvitkovich, E. Dassie, C. F. Vogelaar, A. Faissner, B. Blits, F. H. Gage, C. ffrench-Constant, and J. W. Fawcett {alpha}9 Integrin Promotes Neurite Outgrowth on Tenascin-C and Enhances Sensory Axon Regeneration J. Neurosci., April 29, 2009; 29(17): 5546 - 5557. [Abstract] [Full Text] [PDF]

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