WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience MBF Bioscience Autoneuron
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, January 30, 2008, 28(5):1262-1269; doi:10.1523/JNEUROSCI.1068-07.2008

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hu, F.
Right arrow Articles by Strittmatter, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hu, F.
Right arrow Articles by Strittmatter, S. M.

 Previous Article

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

Fenghua Hu1,2 and Stephen M. Strittmatter1,2

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

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






-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2008 by Society for Neuroscience ONLINE ISSN: 1529-2401
-