title: The Adhesion Molecule KAL-1/anosmin-1 Regulates Neurite Branching through a SAX-7/L1CAM-EGL-15/FGFR Receptor Complex.
abstract: Neurite branching is essential for correct assembly of neural circuits, yet it remains a poorly understood process. For example, the neural cell adhesion molecule KAL-1/anosmin-1, which is mutated in Kallmann syndrome, regulates neurite branching through mechanisms largely unknown. Here, we show that KAL-1/anosmin-1 mediates neurite branching as an autocrine co-factor with EGL-17/FGF through a receptor complex consisting of the conserved cell adhesion molecule SAX-7/L1CAM and the fibroblast growth factor receptor EGL-15/FGFR. This protein complex, which appears conserved in humans, requires the immunoglobulin (Ig) domains of SAX-7/L1CAM and the FN(III) domains of KAL-1/anosmin-1 for formation in vitro as well as function in vivo. The kinase domain of the EGL-15/FGFR is required for branching, and genetic evidence suggests that ras-mediated signaling downstream of EGL-15/FGFR is necessary to effect branching. Our studies establish a molecular pathway that regulates neurite branching during development of the nervous system.
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Díaz-Balzac
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: María I
authors.initials: MI
authors.lastname: Lázaro-Peña
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Biology, University of Puerto Rico-Río Piedras, San Juan 00931, Puerto Rico.
authors.forename: Gibram A
authors.initials: GA
authors.lastname: Ramos-Ortiz
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: hannes.buelow@einstein.yu.edu.
authors.forename: Hannes E
authors.initials: HE
authors.lastname: Bülow
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D016501:Neurites / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; C112493:EGL-15 protein, C elegans; C513487:KAL-1 protein, C elegans; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D017468:Receptors, Fibroblast Growth Factor; C501528:SAX-7 protein, C elegans