title: Cloning of AL-1, a ligand for an Eph-related tyrosine kinase receptor involved in axon bundle formation.
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.
authors.affiliation: Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Winslow
authors.forename: P
authors.initials: P
authors.lastname: Moran
authors.forename: J
authors.initials: J
authors.lastname: Valverde
authors.forename: A
authors.initials: A
authors.lastname: Shih
authors.forename: J Q
authors.initials: JQ
authors.lastname: Yuan
authors.forename: S C
authors.initials: SC
authors.lastname: Wong
authors.forename: S P
authors.initials: SP
authors.lastname: Tsai
authors.forename: A
authors.initials: A
authors.lastname: Goddard
authors.forename: W J
authors.initials: WJ
authors.lastname: Henzel
authors.forename: F
authors.initials: F
authors.lastname: Hefti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D003001:Cloning, Molecular; D036383:Ephrin-A2; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D007074:Immunoglobulin G; D008024:Ligands; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D036383:Ephrin-A2; D007074:Immunoglobulin G; D008024:Ligands; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D020794:Receptor Protein-Tyrosine Kinases