CLONING OF AL-1, A LIGAND FOR AN EPH-RELATED TYROSINE KINASE RECEPTORINVOLVED IN AXON BUNDLE FORMATION

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