Neurite outgrowth by the alternatively spliced region of human tenascin-C is mediated by neuronal alpha7beta1 integrin


The region of tenascin-C containing only alternately spliced fibronectin type-III repeat D (fnD) increases neurite outgrowth by itself and also as part of tenascin-C. We previously localized the active site within fnD to an eight amino acid sequence unique to tenascin-C, VFDNFVLK, and showed that the amino acids FD and FV are required for activity. The purpose of this study was to identify the neuronal receptor that interacts with VFDNFVLK and to investigate the hypothesis that FD and FV are important for receptor binding. Function-blocking antibodies against both alpha7 and beta1 integrin subunits were found to abolish VFDNFVLK-mediated process extension from cerebellar granule neurons. VFDNFVLK but not its mutant, VSPNGSLK, induced clustering of neuronal beta1 integrin immunoreactivity. This strongly implicates FD and FV as important structural elements for receptor activation. Moreover, biochemical experiments revealed an association of the alpha7beta1 integrin with tenascin-C peptides containing the VFDNFVLK sequence but not with peptides with alterations in FD and/or FV. These findings are the first to provide evidence that the alpha7beta1 integrin mediates a response to tenascin-C and the first to demonstrate a functional role for the alpha7beta1 integrin receptor in CNS neurons.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: Copyright © 2004 Society for Neuroscience. Articles are released under a Creative Commons Attribution License after a 6 months embargo
Uncontrolled Keywords: tenascin-C,FN-III repeat,alternatively spliced region,synthetic peptide,site-directed modifications,neurite outgrowth,alpha7beta1,integrin
Publication ISSN: 1529-2401
Last Modified: 12 Jun 2024 07:07
Date Deposited: 14 Sep 2010 11:29
Full Text Link:
Related URLs: http://www.jneu ... stract/24/1/238 (Publisher URL)
PURE Output Type: Article
Published Date: 2004-01-07
Authors: Mercado, Mary L.T.
Nur-E-Kamal, Alam
Liu, Hsing-Yin
Gross, Stephane R. (ORCID Profile 0000-0002-0867-8866)
Movahed, Reza
Meiners, Sally



Version: Published Version

| Preview

Export / Share Citation


Additional statistics for this record