TY - JOUR
T1 - The Adhesion Molecule KAL-1/anosmin-1 Regulates Neurite Branching through a SAX-7/L1CAM-EGL-15/FGFR Receptor Complex
AU - Díaz-Balzac, Carlos A.
AU - Lázaro-Peña, María I.
AU - Ramos-Ortiz, Gibram A.
AU - Bülow, Hannes E.
N1 - Funding Information:
We thank T. Boulin, J. Hébert, R. Townley, and members of the Bülow laboratory for comments on the manuscript and for discussion during the course of this work; J. Culotti, O. Hobert, K. Shen, and R. Pocock for DNA clones; the Caenorhabditis Genetics Center (CGC) for strains; and M. Akabas for use of his cell culture facility. This work was funded in part through the NIH (R01HD055380 and R01GM101313 to H.E.B.; T32GM007288 and F31HD066967 to C.A.D.B.; T32GM07491 to M.I.L.P.; P30HD071593 to Albert Einstein College of Medicine; and P40 OD010440 to the CGC) and a Human Genome Pilot Project from Albert Einstein College of Medicine. H.E.B. is an Alfred P. Sloan and Irma T. Hirschl/Monique Weill-Caulier research fellow.
Publisher Copyright:
© 2015 The Authors.
PY - 2015/6/9
Y1 - 2015/6/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84930758387&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930758387&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2015.04.057
DO - 10.1016/j.celrep.2015.04.057
M3 - Article
C2 - 26004184
AN - SCOPUS:84930758387
SN - 2211-1247
VL - 11
SP - 1377
EP - 1384
JO - Cell Reports
JF - Cell Reports
IS - 9
ER -