Pathological missense mutations of neural cell adhesion molecule L1 affect neurite outgrowth and branching on an L1 substrate

Ling Cheng, Vance Lemmon

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

A number of pathological missense mutations of L1CAM have been shown to disrupt L1-L1 homophilic binding and/or affect surface expression. To investigate whether these mutations disrupt L1-mediated neurite outgrowth, cerebellar neurons from L1 knockout mice are transfected with WT human L1 or L1 mutant constructs, and grown on an L1 substrate. Various parameters of neurite growth are quantified. Most L1mutations do not affect neurite length significantly but several mutations cause a significant decrease in branching. Comparison of these data with data on L1 expression levels and homophilic binding strength show that changes in neurite growth cannot be simply explained by reductions in either of these parameters. Our results suggest that a coreceptor is involved in L1-mediated neurite outgrowth. Some pathological mutations have little effect on L1 mediated neurite growth, so it is unlikely that a failure of L1-mediated neurite outgrowth is the principle cause of brain defects in patients with L1 mutations.

Original languageEnglish
Pages (from-to)522-530
Number of pages9
JournalMolecular and Cellular Neuroscience
Volume27
Issue number4
DOIs
StatePublished - Dec 1 2004

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Neural Cell Adhesion Molecule L1
Neurites
Missense Mutation
Mutation
Growth
Knockout Mice
Neurons
Neuronal Outgrowth
Brain

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

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