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

Mary L.T. Mercado, Alam Nur-E-Kamal, Hsing-Yin Liu, Stephane R. Gross, Reza Movahed, Sally Meiners

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)238-247
Number of pages10
JournalJournal of Neuroscience
Volume24
Issue number1
DOIs
Publication statusPublished - 7 Jan 2004

Fingerprint

Tenascin
CD29 Antigens
Neurons
Blocking Antibodies
C-Peptide
Fibronectins
Cluster Analysis
Amino Acid Sequence
Catalytic Domain
integrin alpha7beta1
valyl-phenylalanyl-aspartyl-norleucyl-phenylalanyl-valyl-leucyl-arginine
Neuronal Outgrowth
Amino Acids
Peptides

Bibliographical note

Copyright © 2004 Society for Neuroscience. Articles are released under a Creative Commons Attribution License after a 6 months embargo

Keywords

  • tenascin-C
  • FN-III repeat
  • alternatively spliced region
  • synthetic peptide
  • site-directed modifications
  • neurite outgrowth
  • alpha7beta1
  • integrin

Cite this

Mercado, Mary L.T. ; Nur-E-Kamal, Alam ; Liu, Hsing-Yin ; Gross, Stephane R. ; Movahed, Reza ; Meiners, Sally. / Neurite outgrowth by the alternatively spliced region of human tenascin-C is mediated by neuronal alpha7beta1 integrin. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 1. pp. 238-247.
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Neurite outgrowth by the alternatively spliced region of human tenascin-C is mediated by neuronal alpha7beta1 integrin. / Mercado, Mary L.T.; Nur-E-Kamal, Alam; Liu, Hsing-Yin; Gross, Stephane R.; Movahed, Reza; Meiners, Sally.

In: Journal of Neuroscience, Vol. 24, No. 1, 07.01.2004, p. 238-247.

Research output: Contribution to journalArticle

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T1 - Neurite outgrowth by the alternatively spliced region of human tenascin-C is mediated by neuronal alpha7beta1 integrin

AU - Mercado, Mary L.T.

AU - Nur-E-Kamal, Alam

AU - Liu, Hsing-Yin

AU - Gross, Stephane R.

AU - Movahed, Reza

AU - Meiners, Sally

N1 - Copyright © 2004 Society for Neuroscience. Articles are released under a Creative Commons Attribution License after a 6 months embargo

PY - 2004/1/7

Y1 - 2004/1/7

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KW - alpha7beta1

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JF - Journal of Neuroscience

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