Neuroglian activates Echinoid to antagonize the Drosophila EGF receptor signaling pathway.
echinoid (ed) encodes an cell-adhesion molecule (CAM) that contains immunoglobulin domains and regulates the EGFR signaling pathway during Drosophila eye development. Based on our previous genetic mosaic and epistatic analysis, we proposed that Ed, via homotypic interactions, activates a novel, as yet unknown pathway that antagonizes EGFR signaling. In this report, we demonstrate that Ed functions as a homophilic adhesion molecule and also engages in a heterophilic trans-interaction with Drosophila Neuroglian (Nrg), an L1-type CAM. Co-expression of ed and nrg in the eye exhibits a strong genetic synergy in inhibiting EGFR signaling. This synergistic effect requires the intracellular domain of Ed, but not that of Nrg. In addition, Ed and Nrg colocalize in the Drosophila eye and are efficiently co-immunoprecipitated. Together, our results suggest a model in which Nrg acts as a heterophilic ligand and activator of Ed, which in turn antagonizes EGFR signaling.
Islam
Rafique
R
Department of Cell and Developmental Biology, University of Michigan, Medical School, Ann Arbor, MI 48109-0616, USA.
Wei
Shu-Yi
SY
Chiu
Wei-Hsin
WH
Hortsch
Michael
M
Hsu
Jui-Chou
JC
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002449:Cell Aggregation / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism*; D008954:Models, Biological; D017956:Photoreceptor Cells, Invertebrate / Q000033:anatomy & histology / Q000254:growth & development; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; C422623:ED protein, Drosophila; D012097:Repressor Proteins; C061745:Nrg protein, Drosophila; D066246:ErbB Receptors