Reference Report

Reference
Citation	Molnar, C., Ruiz-Gómez, A., Martín, M., Rojo-Berciano, S., Mayor, F., de Celis, J.F. (2011). Role of the Drosophila non-visual ß-arrestin kurtz in hedgehog signalling. PLoS Genet. 7(3): e1001335. (Export to RIS)
FlyBase ID	FBrf0213301
Publication Type	Research paper
PubMed ID	21437272
PubMed Abstract	The non-visual ß-arrestins are cytosolic proteins highly conserved across species that participate in a variety of signalling events, including plasma membrane receptor degradation, recycling, and signalling, and that can also act as scaffolding for kinases such as MAPK and Akt/PI3K. In Drosophila melanogaster, there is only a single non-visual ß-arrestin, encoded by kurtz, whose function is essential for neuronal activity. We have addressed the participation of Kurtz in signalling during the development of the imaginal discs, epithelial tissues requiring the activity of the Hedgehog, Wingless, EGFR, Notch, Insulin, and TGFβ pathways. Surprisingly, we found that the complete elimination of kurtz by genetic techniques has no major consequences in imaginal cells. In contrast, the over-expression of Kurtz in the wing disc causes a phenotype identical to the loss of Hedgehog signalling and prevents the expression of Hedgehog targets in the corresponding wing discs. The mechanism by which Kurtz antagonises Hedgehog signalling is to promote Smoothened internalization and degradation in a clathrin- and proteosomal-dependent manner. Intriguingly, the effects of Kurtz on Smoothened are independent of Gprk2 activity and of the activation state of the receptor. Our results suggest fundamental differences in the molecular mechanisms regulating receptor turnover and signalling in vertebrates and invertebrates, and they could provide important insights into divergent evolution of Hedgehog signalling in these organisms.
DOI	10.1371/journal.pgen.1001335
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Language of Publication	English
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Publication Type	Journal
Abbreviation	PLoS Genet.
Title	PLoS Genetics
Publication Year	2005-
ISBN/ISSN	1553-7404 1553-7390
Data from Reference
Aberrations (2)
	Df(3R)Gprk2 Df(3R)krz
Alleles (38)
	Avic\GFP^Scer\UAS.cUa CG32683^{dsRNA.Scer\UAS} CG32683^{Scer\UAS.T:Zzzz\FLAG} cos^Scer\UAS.cUa Dcr-2^Scer\UAS.cDa Egfr^{DN.Scer\UAS.cBa} Gprk2^{dsRNA.Scer\UAS} hh^NIG.4637R krz^d1 krz^{dsRNA.Scer\UAS} krz^{Leu.Scer\UAS.T:Zzzz\FLAG} krz^{S427D.Scer\UAS.T:Zzzz\FLAG} krz^S047819 krz^Scer\UAS.cMa krz^{Scer\UAS.T:Zzzz\FLAG} krz^{V94D.Scer\UAS.T:Zzzz\FLAG} M(2)58F¹ mod^d1 N^{int.G.Scer\UAS} N^NIG.3936R RpS3¹ Scer\FLP1^hs.PG Scer\FLP1^Scer\UAS.cUa Scer\GAL4^ap-md544 Scer\GAL4^dpp.blk1 Scer\GAL4^MD-638 Scer\GAL4^nub-AC-62 Scer\GAL4^salm.EPv Scer\GAL4^{Scer\FRT.Act5C} Scer\GAL4^unspecified Scer\GAL4^wor.PA Scer\GAL80^αTub84B.PL smo² smo^{C.Scer\UAS.T:Avic\GFP-CFP} smo^{CKI.Scer\UAS.T:Zzzz\FLAG} smo^{PKA123.Scer\UAS.T:Zzzz\FLAG} smo^{Scer\UAS.J.T:Zzzz\FLAG} smo^{SD123.Scer\UAS.T:Zzzz\FLAG}
Constructs (29)
	P{AyGAL4} P{GAL4} P{GAL4-dpp.blk1} P{hsFLP} P{NIG.3936R} P{NIG.4637R} P{salm-GAL4.EPv} P{tubP-GAL80} P{UAS.Gprk2.dsRNA} P{UAS-CG32683.FLAG} P{UAS-CG32683.RNAi} P{UAS-cos.U} P{UAS-Dcr-2.D} P{UAS-Egfr.DN.B} P{UAS-FLP1.U} P{UAS-GFP.U} P{UAS-krz.FLAG.Leu} P{UAS-krz.FLAG.S427D} P{UAS-krz.FLAG.V94D} P{UAS-krz.FLAG} P{UAS-krz.M} P{UAS-krz.RNAi} P{UAS-N.intra.G} P{UAS-smo.CFP.C} P{UAS-smo.Fg.CKI} P{UAS-smo.Fg.PKA123} P{UAS-smo.Fg.SD123} P{UAS-smo.Fg} P{wor.GAL4.A}
Genes (20)
	Avic\GFP CG32683 cos Dcr-2 Egfr en Fas3 Gprk2 hh krz M(2)58F mod N ptc RpS3 Scer\FLP1 Scer\GAL4 Scer\GAL80 smo T:Zzzz\FLAG
Insertions (5)
	P{GAL4}MD-638 P{GawB}ap^md544 P{GawB}nubbin-AC-62 PBac{RB}krz^e03507 PBac{RB}mod^e00739
Natural transposons (1)
	P-element