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