The L1 adhesion molecule is a cellular ligand for VLA-5

J Cell Biol. 1995 Dec;131(6 Pt 2):1881-91. doi: 10.1083/jcb.131.6.1881.


The L1 adhesion molecule is a member of the immunoglobulin superfamily shared by neural and immune cells. In the nervous system L1 can mediate cell binding by a homophilic mechanism. To analyze its function on leukocytes we studied whether L1 could interact with integrins. Here we demonstrate that VLA-5, an RGD-specific fibronectin receptor on a wide variety of cell types, can bind to murine L1. Mouse ESb-MP cells expressing VLA-5 and L1 could be induced to aggregate in the presence of specific mAbs to CD24 (heat-stable antigen), a highly and heterogeneously glycosylated glycophosphatidylinositol-linked differentiation antigen of hematopoietic and neural cells. The aggregation was blocked by both mAbs to L1 and VLA-5, respectively. Aggregation was blocked also by a synthetic RGD-containing peptide derived from the Ig-domain VI of the L1 protein. ESb-MP subclones with low L1 expression could not aggregate. In heterotypic binding assays mouse bone marrow cells could adhere in an L1-dependent fashion to platelets that expressed VLA-5. Also purified L1 coated to polystyrene beads could bind to platelets. The binding of L1-beads was again inhibited by mAbs to L1 and VLA-5, by soluble L1 and the L1-RGD peptide in a dose-dependent manner. Thymocytes or human Nalm-6 tumor cells expressing VLA-5 could adhere to affinity-purified L1 and to the L1-derived RGD-containing peptide coated to glass slides. The adhesion was strongly enhanced in the presence of Mn(2+)-ions and blocked by mAbs to VLA-5. We also demonstrate a direct L1-VLA-5 protein interaction. Our results suggest a novel binding pathway, in which the VLA-5 integrin binds to L1 on adjacent cells. Given its rapid downregulation on lymphocytes after induction of cell proliferation, L1 may be important in integrin-mediated and activation-regulated cell-cell interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • Antifungal Agents / metabolism*
  • Blood Platelets / cytology
  • Bone Marrow Cells
  • Cell Adhesion / physiology
  • Cell Aggregation / physiology
  • Endothelium, Vascular / cytology
  • Humans
  • Leukocyte L1 Antigen Complex
  • Mice
  • Molecular Sequence Data
  • Monocytes / cytology
  • Neural Cell Adhesion Molecules / isolation & purification
  • Neural Cell Adhesion Molecules / metabolism*
  • Oligopeptides / isolation & purification
  • Oligopeptides / metabolism
  • Receptors, Fibronectin / immunology
  • Receptors, Fibronectin / metabolism*
  • Thymus Gland / cytology
  • Tumor Cells, Cultured / metabolism


  • Antibodies, Monoclonal
  • Antifungal Agents
  • Leukocyte L1 Antigen Complex
  • Neural Cell Adhesion Molecules
  • Oligopeptides
  • Receptors, Fibronectin
  • arginyl-glycyl-aspartic acid