Reference Report

Reference
Citation	Herranz, H., Stamataki, E., Feiguin, F., Milan, M. (2006). Self-refinement of Notch activity through the transmembrane protein Crumbs: modulation of gamma-Secretase activity. EMBO Rep. 7(3): 297--302. (Export to RIS)
FlyBase ID	FBrf0190373
Publication Type	Research paper
PubMed ID	16440003
PubMed Abstract	Cell interactions mediated by Notch family receptors have been implicated in the specification of tissue boundaries. Tightly localized activation of Notch is crucial for the formation of sharp boundaries. In the Drosophila wing imaginal disc, the Notch receptor is expressed in all cells. However, Notch activity is limited to a narrow stripe of cells along the dorsal-ventral compartment boundary, where it induces the expression of target genes. How a widely expressed protein becomes tightly regulated at the dorsal-ventral boundary in the Drosophila wing is not completely understood. Here, we show that the transmembrane protein Crumbs is involved in a feedback mechanism used by Notch to refine its own activation domain at the Drosophila wing margin. Crumbs reduces the activity of the gamma-Secretase complex, which mediates the proteolytic intracellular processing of Notch. These results indicate a novel molecular mechanism of the regulation of Notch signal, and also that defects in Crumbs might be involved in similar abnormal gamma-Secretase complex activity observed in Alzheimer's disease.
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Supplementary material	Supplementary Methods. [FBrf0211302]
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Language of Publication	English
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Publication Type	Journal
Abbreviation	EMBO Rep.
Title	EMBO Reports
Publication Year	2000-
ISBN/ISSN
Data from Reference
Aberrations (1)
	Df(1)N-8
Alleles (25)
	Avic\GFP^Scer\UAS.cUa crb^8F105 crb^11A22 crb^{extraTM.Scer\UAS.T:Avic\GFP} crb^M11.M2 crb^Scer\UAS.cWa Dl^{DN.cHa.Scer\UAS} Ecol\lacZ^crb-M11.M2 Ecol\lacZ^wg-en11 grim^Scer\UAS.cYa H^Scer\UAS.cGa Hsap\APP^{Δ.hs.T:Scer\GAL4,T:Hsim\VP16} mam^EPgJ3-285 N^Ax-M1 N^Co N^{ECN.hs.T:Scer\GAL4,T:Hsim\VP16} N^{ECN.Scer\UAS.cGa} N^{int.U.Scer\UAS} N^l1N-ts2 Scer\GAL4^ap-md544 Scer\GAL4^dpp.blk1 Scer\GAL4^{GMR.T:Hsap\APP} Scer\GAL4^ptc-559.1 sdt^XP Ser^{DN.cHa.Scer\UAS}
Constructs (10)
	P{GAL4-dpp.blk1} P{GMR-APP-GAL4} P{hs-N^ECN-GV} P{hs-Δβ-APP-GV} P{UAS-Dl.DN.H} P{UAS-GFP.U} P{UAS-grim.Y} P{UAS-H.G} P{UAS-N.intra.U} P{UAS-Ser.DN.H}
Genes (15)
	Avic\GFP crb ct Dl Ecol\lacZ grim H Hsap\APP mam N Scer\GAL4 sdt sens Ser wg
Insertions (5)
	P{en1}wg^en11 P{EPg}mam^EPgJ3-285 P{GawB}ap^md544 P{GawB}ptc^559.1 PBac{nub-lacZ.A}crb^M11.M2
Natural transposons (1)
	P-element