Unidirectional Notch signaling depends on continuous cleavage of Delta.
Unidirectional signaling from cells expressing Delta (Dl) to cells expressing Notch is a key feature of many developmental processes. We demonstrate that the Drosophila ADAM metalloprotease Kuzbanian-like (Kul) plays a key role in promoting this asymmetry. Kul cleaves Dl efficiently both in cell culture and in flies, and has previously been shown not to be necessary for Notch processing during signaling. In the absence of Kul in the developing wing, the level of Dl in cells that normally receive the signal is elevated, and subsequent alterations in the directionality of Notch signaling lead to prominent phenotypic defects. Proteolytic cleavage of Dl by Kul represents a general mechanism for refining and maintaining the asymmetric distribution of Dl, in cases where transcriptional repression of Dl expression does not suffice to eliminate Dl protein.
Sapir
Amir
A
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Assa-Kunik
Efrat
E
Tsruya
Rachel
R
Schejter
Eyal
E
Shilo
Ben-Zion
BZ
D000818:Animals; D002478:Cells, Cultured; D019483:Disintegrins / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism / Q000502:physiology*; D045726:Metalloproteases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D010802:Phylogeny; D011485:Protein Binding; D051880:Receptors, Notch; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D014921:Wings, Animal / Q000196:embryology / Q000378:metabolism
D019483:Disintegrins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C064045:delta protein; D045726:Metalloproteases; C100953:KUZ protein, Drosophila; C496880:Kul protein, Drosophila; D008666:Metalloendopeptidases