A conserved role for L1 as a transmembrane link between neuronal adhesion and membrane cytoskeleton assembly

Cell Adhes Commun. 1998 Jan;5(1):61-73. doi: 10.3109/15419069809005599.


The L1-family of cell adhesion molecules is involved in many important aspects of nervous system development. Mutations in the human L1-CAM gene cause a complicated array of neurological phenotypes; however, the molecular basis of these effects cannot be explained by a simple loss of adhesive function. Human L1-CAM and its Drosophila homolog neuroglian are rather divergent in sequence, with the highest degree of amino acid sequence conservation between segments of their cytoplasmic domains. In an attempt to elucidate the fundamental functions shared between these distantly related members of the L1-family, we demonstrate here that the extracellular domains of mammalian L1-CAMs and Drosophila neuroglian are both able to induce the aggregation of transfected Drosophila S2 cells in vitro. To a limited degree they even interact with each other in cell adhesion and neurite outgrowth assays. The cytoplasmic domains of human L1-CAM and neuroglian are both able to interact with the Drosophila homolog of the cytoskeletal linker protein ankyrin. Moreover the recruitment of ankyrin to cell-cell contacts is completely dependent on L1-mediated cell adhesion. These findings support a model of L1 function in which the phenotypes of human L1-CAM mutations results from a disruption of the link between the extracellular environment and the neuronal cytoskeleton.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Ankyrins / metabolism
  • Cell Adhesion Molecules, Neuronal / chemistry
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cell Adhesion Molecules, Neuronal / pharmacology*
  • Cell Aggregation / drug effects
  • Cells, Cultured
  • Cerebellar Cortex / cytology
  • Cytoskeleton / physiology*
  • Cytoskeleton / ultrastructure
  • DNA, Complementary / genetics
  • Drosophila Proteins
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Humans
  • Insect Proteins / chemistry
  • Insect Proteins / metabolism
  • Insect Proteins / pharmacology
  • Leukocyte L1 Antigen Complex
  • Macromolecular Substances
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / pharmacology*
  • Mice
  • Microscopy, Fluorescence
  • Neural Cell Adhesion Molecules / chemistry
  • Neural Cell Adhesion Molecules / genetics
  • Neural Cell Adhesion Molecules / metabolism
  • Neural Cell Adhesion Molecules / pharmacology*
  • Neurites / physiology
  • Phenotype
  • Recombinant Fusion Proteins / physiology
  • Saccharomyces cerevisiae / genetics
  • Species Specificity
  • Transfection


  • Ankyrins
  • Cell Adhesion Molecules, Neuronal
  • DNA, Complementary
  • Drosophila Proteins
  • Insect Proteins
  • Leukocyte L1 Antigen Complex
  • Macromolecular Substances
  • Membrane Glycoproteins
  • Neural Cell Adhesion Molecules
  • Recombinant Fusion Proteins
  • Nrg protein, Drosophila