Identification of the border between fibronectin type III homologous repeats 2 and 3 of the neural cell adhesion molecule L1 as a neurite outgrowth promoting and signal transducing domain

Frank Appel, Jürgen Holm, Jean‐François ‐F Conscience, Friedrich von Bohlen, Halbach, Andreas Faissner, Peter James, Melitta Schachner

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

To determine the domains of the neural cell adhesion molecule L1 involved in neurite outgrowth, we have generated monoclonal antibodies against L1 and investigated their effects on neurite outgrowth of small cerebellar neurons in culture. When the 10 antibodies were coated as substrate, only antibody 557.B6, which recognizes an epitope represented by a synthetic peptide comprising amino acids 818 to 832 at the border between the fibronectin type III homologous repeats 2 and 3, was as efficacious as L1 in promoting neurite outgrowth, increasing intracellular levels of Ca2+, and stimulating the turnover of inositol phosphates. These findings suggest that neurite outgrowth and changes in these second messengers are correlated. Such a correlation was confirmed by the ability of Ca2+ channel antagonists and pertussis toxin to inhibit neurite outgrowth on L1 and antibody 557.B6. These observations indicate for the first time a distinct site on cell surface‐bound‐L1 as a prominent signal‐transducing domain through which the recognition events appear to be funneled to trigger neurite outgrowth, increase turnover of inositol phosphates, and elevate intracellular levels of Ca2+. © 1995 John Wiley & Sons, Inc.

Original languageEnglish (US)
Pages (from-to)297-312
Number of pages16
JournalJournal of Neurobiology
Volume28
Issue number3
DOIs
StatePublished - Nov 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

Keywords

  • L1
  • fibronectin type III homologous repeats
  • inositol phosphates
  • neurite outgrowth
  • signal transduction

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