Single chain Fv antibodies against neural cell adhesion molecule L1 trigger L1 functions in cultured neurons

Ling Dong, Suzhen Chen, Melitta Camartin

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The neural cell adhesion molecule L1 plays important roles in cell adhesion, neuronal migration, neurite outgrowth, fasciculation and pathfinding, neuronal survival, and synaptic plasticity. Many of these functions have been identified and characterized by using antibodies. Because of the need for reproducible and functionally active antibodies, we have generated two single-chain variable fragment antibodies against mouse L1 from a human synthetic phage display library. The complementarity determining region 3 of the variable heavy chains of the two antibodies differed in length and sequence. Both antibodies recognized mouse, but not human L1, by enzyme-linked immunosorbent assay, Western blot, and immunofluorescence staining of cultured neurons. Epitope mapping showed reactivity with the fibronectin type III repeats 1-2 of mouse L1. The antibodies stimulated neurite outgrowth from cerebellar dorsal, root ganglion and motor neurons when offered in substrate-coated form in a dose-dependent manner with maximal effects at approximately 32 nM. Furthermore, substrate-coated antibodies enhanced survival of cerebellar neurons. Peptides comprising 8 and 11 amino acids derived from the complementarity determining region 3 of the variable heavy chains of the two single-chain variable fragment antibodies also promoted neurite outgrowth. The combined observations indicate that single-chain variable fragment antibodies against L1 and peptides derived from their binding domains can mimic some beneficial functions of homophilically binding L1 in vitro and may thus serve to trigger these functions in vivo.

Original languageEnglish (US)
Pages (from-to)234-247
Number of pages14
JournalMolecular and Cellular Neuroscience
Volume22
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

Fingerprint

Neural Cell Adhesion Molecule L1
Single-Chain Antibodies
Neurons
Antibodies
Complementarity Determining Regions
Neuronal Plasticity
Epitope Mapping
Peptides
Spinal Ganglia
Motor Neurons
Fibronectins
Cell Adhesion
Bacteriophages
Libraries
Fluorescent Antibody Technique
Western Blotting
Enzyme-Linked Immunosorbent Assay
Staining and Labeling
Amino Acids

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

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abstract = "The neural cell adhesion molecule L1 plays important roles in cell adhesion, neuronal migration, neurite outgrowth, fasciculation and pathfinding, neuronal survival, and synaptic plasticity. Many of these functions have been identified and characterized by using antibodies. Because of the need for reproducible and functionally active antibodies, we have generated two single-chain variable fragment antibodies against mouse L1 from a human synthetic phage display library. The complementarity determining region 3 of the variable heavy chains of the two antibodies differed in length and sequence. Both antibodies recognized mouse, but not human L1, by enzyme-linked immunosorbent assay, Western blot, and immunofluorescence staining of cultured neurons. Epitope mapping showed reactivity with the fibronectin type III repeats 1-2 of mouse L1. The antibodies stimulated neurite outgrowth from cerebellar dorsal, root ganglion and motor neurons when offered in substrate-coated form in a dose-dependent manner with maximal effects at approximately 32 nM. Furthermore, substrate-coated antibodies enhanced survival of cerebellar neurons. Peptides comprising 8 and 11 amino acids derived from the complementarity determining region 3 of the variable heavy chains of the two single-chain variable fragment antibodies also promoted neurite outgrowth. The combined observations indicate that single-chain variable fragment antibodies against L1 and peptides derived from their binding domains can mimic some beneficial functions of homophilically binding L1 in vitro and may thus serve to trigger these functions in vivo.",
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Single chain Fv antibodies against neural cell adhesion molecule L1 trigger L1 functions in cultured neurons. / Dong, Ling; Chen, Suzhen; Camartin, Melitta.

In: Molecular and Cellular Neuroscience, Vol. 22, No. 2, 01.02.2003, p. 234-247.

Research output: Contribution to journalArticle

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