The metalloprotease-disintegrin Kuzbanian participates in Notch activation during growth and patterning of Drosophila imaginal discs.
The Notch transmembrane protein is the receptor of an evolutionary conserved pathway that mediates intercellular signalling leading to the specification of different cell types during development. In this pathway, many aspects of the signal transduction mechanism remain poorly understood, especially the role of proteolytic processing of Notch. We present genetic evidence indicating that the metalloprotease-disintegrin kuzbanian (J. Rooke, D. Pan, T. Xu and G. M. Rubin (1996) Science 273, 1227-1231) is a new component of the Notch signalling pathway and is involved in Notch activation. kuzbanian genetic mosaics demonstrate that, during neurogenesis, wing margin formation and vein width specification kuzbanian is autonomously required in the cell where Notch is activated. Genetic interactions between kuzbanian and different genes of the Notch pathway indicate that kuzbanian is required upstream of Suppressor of Hairless. Moreover, the requirement of kuzbanian for signalling by a ligand-dependent Abruptex receptor, but not by a constitutively activated form of Notch, suggests that kuzbanian is involved in the generation of a Notch functional receptor and/or in its activation. However, differences in the phenotypes of loss-of-function Notch and kuzbanian mutations suggest the existence of alternative Kuzbanian-independent mechanisms that generate Notch functional receptors.
Sotillos
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Centro de Biología Molecular Severo Ochoa, CSIC and UAM, Madrid, Spain.
Roch
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Campuzano
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D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning / Q000235:genetics; D002135:Calcium-Binding Proteins; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019483:Disintegrins / Q000235:genetics* / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology* / Q000235:genetics / Q000254:growth & development; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D007814:Larva / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors; D014921:Wings, Animal / Q000196:embryology
D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D019483:Disintegrins; D029721:Drosophila Proteins; D019476:Insect Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D008666:Metalloendopeptidases; D051880:Receptors, Notch; D012097:Repressor Proteins; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors; C084530:E(spl)mdelta-HLH protein, Drosophila; C497759:N protein, Drosophila; C000606278:Ser protein, Drosophila; C088731:Su(H) protein, Drosophila; C076560:H protein, Drosophila; C100953:KUZ protein, Drosophila