Fringe forms a complex with Notch.
The Fringe protein of Drosophila and its vertebrate homologues function in boundary determination during pattern formation. Fringe has been proposed to inhibit Serrate-Notch signalling but to potentiate Delta-Notch signalling. Here we show that Fringe and Notch form a complex through both the Lin-Notch repeats and the epidermal growth factor repeats 22-36 (EGF22-36) of Notch when they are co-expressed. The Abruptex59b (Ax59b) and AxM1 mutations, which are caused by missense mutations in EGF repeats 24 and 25, respectively, abolish the Fringe-Notch interaction through EGF22-36, whereas the l(1)N(B) mutation in the third Lin-Notch repeat of Notch abolishes the interaction through Lin-Notch repeats. Ax mutations also greatly affect the Notch response to ectopic Fringe in vivo. Results from in vitro protein mixing experiments and subcellular colocalization experiments indicate that the Fringe-Notch complex may form before their secretion. These findings explain how Fringe acts cell-autonomously to modulate the ligand preference of Notch and why the Fringe-Notch relationship is conserved between phyla and in the development of very diverse structures.
Ju
B G
BG
National Creative Research Initiative Center for Genetic Reprogramming, Institute of Molecular Biology and Genetics, Seoul National University, Korea.
Jeong
S
S
Bae
E
E
Hyun
S
S
Carroll
S B
SB
Yim
J
J
Kim
J
J
D000818:Animals; D002460:Cell Line; D004330:Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases; D011485:Protein Binding; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid
D029721:Drosophila Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins; D017351:N-Acetylglucosaminyltransferases; C090576:fng protein, Drosophila