The Adhesion Molecule KAL-1/anosmin-1 Regulates Neurite Branching through a SAX-7/L1CAM–EGL-15/FGFR Receptor Complex

Autor: Carlos A. Díaz-Balzac, María I. Lázaro-Peña, Gibram A. Ramos-Ortiz, Hannes E. Bülow
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Cell Reports, Vol 11, Iss 9, Pp 1377-1384 (2015)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2015.04.057
Popis: 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.
Databáze: Directory of Open Access Journals