Cloning of AL-1, a Ligand for an Eph-related Tyrosine Kinase Receptor Involved in Axon Bundle Formation

Neuron. 1995 May;14(5):973-81. doi: 10.1016/0896-6273(95)90335-6.

Abstract

REK7 is an Eph-related tyrosine kinase receptor expressed exclusively in the nervous system, predominantly in hippocampus and cortex. A soluble REK7-IgG fusion protein, produced to analyze the biological role of REK7, prevents axon bundling in cocultures of cortical neurons with astrocytes, a model of late stage nervous system development and differentiation. Using REK7-IgG as an affinity reagent, we purified and cloned a novel REK7 ligand called AL-1, a GPI-linked protein homologous to other members of an emerging ligand family. Membrane attachment of AL-1 appears necessary for receptor activation, since REK7 on cortical neurons is efficiently activated by transfected cells expressing GPI-linked AL-1, but not by soluble AL-1. Consistent with this, soluble AL-1 blocks axon bundling. Our findings, together with the observation that both molecules are expressed in the brain, suggest a role in the formation of neuronal pathways, a crucial feature of nervous system development and regeneration.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Axons / drug effects
  • Axons / physiology
  • Axons / ultrastructure*
  • Base Sequence
  • Blotting, Northern
  • Brain / metabolism*
  • Brain / ultrastructure
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cerebral Cortex / embryology
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / ultrastructure
  • Cloning, Molecular*
  • Ephrin-A2
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Hippocampus / metabolism
  • Hippocampus / ultrastructure
  • Immunoglobulin G
  • Ligands
  • Molecular Sequence Data
  • Rats
  • Rats, Wistar
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Recombinant Fusion Proteins
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Ephrin-A2
  • Immunoglobulin G
  • Ligands
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Receptor Protein-Tyrosine Kinases

Associated data

  • GENBANK/S77167