Reference Report

Reference
Citation	Zhu, A.J., Zheng, L., Suyama, K., Scott, M.P. (2003). Altered localization of Drosophila Smoothened protein activates Hedgehog signal transduction. Genes Dev. 17(10): 1240--1252. (Export to RIS)
FlyBase ID	FBrf0159691
Publication Type	Research paper
PubMed ID	12730121
PubMed Abstract	Hedgehog (Hh) signaling is critical for many developmental events and must be restrained to prevent cancer. A transmembrane protein, Smoothened (Smo), is necessary to transcriptionally activate Hh target genes. Smo activity is blocked by the Hh transmembrane receptor Patched (Ptc). The reception of a Hh signal overcomes Ptc inhibition of Smo, activating transcription of target genes. Using Drosophila salivary gland cells in vivo and in vitro as a new assay for Hh signal transduction, we investigated the regulation of Hh-triggered Smo stabilization and relocalization. Hh causes Smo to move from internal membranes to the cell surface. Relocalization is protein synthesis-independent and occurs within 30 min of Hh treatment. Ptc and the kinesin-related protein Costal2 (Cos2) cause internalization of Smo, a process that is dependent on both actin and microtubules. Disruption of endocytosis by dominant negative dynamin or Rab5 prevents Smo internalization. Fly versions of Smo mutants associated with human tumors are constitutively present at the cell surface. Forced localization of Smo at the plasma membrane activates Hh target gene transcription. Conversely, trapping of activated Smo mutants in the ER prevents Hh target gene activation. Control of Smo localization appears to be a crucial step in Hh signaling in Drosophila.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Genes Dev.
Title	Genes & Development
Publication Year	1987-
ISBN/ISSN	0890-9369
Data from Reference
Alleles (31)
	Avic\GFP^{EYFP-ER.Scer\UAS} Avic\GFP^Scer\UAS.cUa Avic\GFP^{Scer\UAS.T:Ocun\LPH-ss,T:Hsap\LFA3-GPI} cos^Scer\UAS.cHa Ecol\lacZ^ptc-H84 hh^hs.PI hh^N.Scer\UAS Khc::nod^{Scer\UAS.T:Ecol\lacZ} ptc^{1130X.Scer\UAS.T:Avic\GFP-YFP} ptc^{1130X.Scer\UAS} ptc^Scer\UAS.cJa ptc^{Scer\UAS.T:Avic\GFP-YFP} Rab5^{S43N.Scer\UAS} Rab7^{Q67L.Scer\UAS} Scer\GAL4^71B Scer\GAL4^Bx-MS1096 Scer\GAL4^da.G32 Scer\GAL4^en-e16E shi^{K44A.Scer\UAS} smo³ smo^{M1.Scer\UAS.T:Avic\GFP,T:Uuuu\KKDE} smo^{M1.Scer\UAS.T:Avic\GFP} smo^{M2.Scer\UAS.T:Avic\GFP,T:Uuuu\KKDE} smo^{M2.Scer\UAS.T:Avic\GFP} smo^{Scer\UAS.cvdHa} smo^{Scer\UAS.T:Avic\GFP,T:Hsap\LFA3-GPI} smo^{Scer\UAS.T:Avic\GFP,T:Hsap\Myr2} smo^{Scer\UAS.T:Avic\GFP} T:Avic\GFP^YFP T:Hsap\LFA3^GPI T:Ocun\LPH^ss
Constructs (23)
	P{GAL4-da.G32} P{HShh.I} P{UAS-cos.H} P{UAS-EYFP-KDEL} P{UAS-GFP.gpi} P{UAS-GFP.U} P{UAS-hh.N} P{UAS-Khc::nod::lacZ} P{UAS-ptc.1130X.YFP} P{UAS-ptc.1130X} P{UAS-ptc.J} P{UAS-ptc.YFP} P{UAS-Rab5.S43N} P{UAS-Rab7.Q67L} P{UAS-shi.K44A} P{UAS-smo.GFP.GAP43} P{UAS-smo.GFP.GPI} P{UAS-smo.GFP} P{UAS-smo.M1.GFP} P{UAS-smo.M1.KKDE.GFP} P{UAS-smo.M2.GFP} P{UAS-smo.M2.KKDE.GFP} P{UAS-smo.vdH}
Genes (18)
	Avic\GFP cos Ecol\lacZ hh Khc::nod ptc Rab5 Rab7 Scer\GAL4 shi smo T:Avic\GFP T:Ecol\lacZ T:Hsap\LFA3 T:Hsap\Myr2 T:Ocun\LPH T:Uuuu\KDEL T:Uuuu\KKDE
Insertions (5)
	P{A92}ptc^H84 P{en2.4-GAL4}e16E P{GawB}71B P{GawB}Bx^MS1096 P{lacZ-un2}ptc-AT90