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PubMed · 10821276

Fringe forms a complex with Notch.

B G Ju·S Jeong·E Bae·S Hyun·S B Carroll·J Yim·J Kim
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Abstract

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.

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AnimalsCell LineDrosophilaDrosophila ProteinsInsect ProteinsMembrane ProteinsMutationN-AcetylglucosaminyltransferasesProtein BindingReceptors, NotchRecombinant Fusion ProteinsRepetitive Sequences, Amino AcidJournal ArticleResearch Support, Non-U.S. Gov't

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B G Ju, S Jeong, E Bae, S Hyun, S B Carroll, J Yim, J Kim. 2000-05-11. Fringe forms a complex with Notch.. https://doi.org/10.1038/35012090

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