Reference Report

Reference
Citation	Wang, W., Struhl, G. (2004). Drosophila Epsin mediates a select endocytic pathway that DSL ligands must enter to activate Notch. Development 131(21): 5367--5380. (Export to RIS)
FlyBase ID	FBrf0180168
Publication Type	Research paper
PubMed ID	15469974
PubMed Abstract	Recent findings suggest that Delta/Serrate/Lag2 (DSL) signals activate Notch by an unprecedented mechanism that requires the ligands to be endocytosed in signal-sending cells to activate the receptor in signal-receiving cells. Here, we show that cells devoid of Epsin, a conserved adaptor protein for Clathrin-mediated endocytosis, behave normally except that they cannot send DSL signals. Surprisingly, we find that Epsin is not required for bulk endocytosis of DSL proteins. Instead, Epsin appears to be essential for targeting DSL proteins to a special endocytic pathway that they must enter to acquire signaling activity. We present evidence that DSL proteins must be mono-ubiquitinated to be targeted by Epsin to this pathway. Furthermore, we show that the requirements for both Epsin and mono-ubiquitination can be bypassed by introducing the internalization signal that mediates endocytosis and recycling of the Low Density Lipoprotein (LDL) receptor. We propose that Epsin is essential for DSL signaling because it targets mono-ubiquitinated DSL proteins to an endocytic recycling compartment that they must enter to be converted into active ligands. Alternatively Epsin may be required to target mono-ubiquitinated DSL proteins to a particular subclass of coated pits that have special properties essential for Notch activation.
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Secondary IDs
Language of Publication	English
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Publication Type	Journal
Abbreviation	Development
Title	Development
Publication Year	1987-
ISBN/ISSN	0950-1991
Data from Reference
Alleles (45)
	Avic\GFP^{Scer\UAS.T:Hsap\MYC,T:SV40\nls2} bi^X35 Dl⁰⁵¹⁵¹ Dl^{m.Scer\UAS.Scer\FRT.T:Hsap\Ubiquitin} Dl^{m.Scer\UAS.T:Hsap\Ubiquitin} Dl^{R.Scer\UAS.Scer\FRT.T:Hsap\MYC} Dl^{R.Scer\UAS.T:Hsap\MYC} Dl^{Rm.Scer\UAS.Scer\FRT.T:Hsap\MYC} Dl^{Rm.Scer\UAS.T:Hsap\MYC} Dl^{Scer\FRT.Scer\UAS.T:Hsap\Ubiquitin} Dl^{Scer\UAS.Scer\FRT.T:Arus\HRP} Dl^{Scer\UAS.Scer\FRT.T:Hsap\LDLR-int,T:Hsap\MYC} Dl^{Scer\UAS.Scer\FRT.T:Hsap\LDLR-int-m,T:Hsap\MYC} Dl^{Scer\UAS.Scer\FRT.T:Hsap\MYC} Dl^{Scer\UAS.T:Arus\HRP} Dl^{Scer\UAS.T:Hsap\LDLR-int,T:Hsap\MYC} Dl^{Scer\UAS.T:Hsap\LDLR-int-m,T:Hsap\MYC} Dl^{Scer\UAS.T:Hsap\MYC} Dl^{Scer\UAS.T:Hsap\Ubiquitin} Dl^{ΔC.Scer\UAS.Scer\FRT.T:Hsap\MYC} Dl^{ΔC.Scer\UAS.T:Hsap\MYC} dpp^Scer\UAS.cNa Ecol\lacZ^arm.PV Ecol\lacZ^bi-X35 Ecol\lacZ^Dl-05151 Ecol\lacZ^dpp.BS3.0 Ecol\lacZ^vg.int2.1 fng^Scer\UAS.cKa hh^{Scer\UAS.T:Ivir\HA1} Hrs^D28 lqf¹²²⁷ lqf^+t19G lqf^ARI lqf^BT Mmus\Cd8a^{Scer\UAS.T:Avic\GFP} neur^Scer\UAS.cLa Scer\GAL4^C-765 Scer\GAL4^{F442A.αTub84B.T:Hsim\VP16} Scer\GAL4^nub-AC-62 Scer\GAL80^αTub84B.PL Ser^Scer\UAS.cSa T:Hsap\LDLR^int T:Hsap\LDLR^int-m wg^l-17 wg^{Scer\UAS.T:Ivir\HA1}
Constructs (31)
	P{arm-lacZ.V} P{BS3.0} P{GAL4-αTub84B(-FRT).VP16^F442A} P{lqf⁺19G} P{tubP-GAL80} P{UAS(FRT.y⁺CD2.A902)Dl.HRP</up>} P{UAS(FRT.y⁺CD2.A902)Dl.LDL+.MYC} P{UAS(FRT.y⁺CD2.A902)Dl.LDLm.MYC} P{UAS(FRT.y⁺CD2.A902)Dl.R.MYC} P{UAS(FRT.y⁺CD2.A902)Dl.T:Hsap\MYC} P{UAS(FRT.y⁺CD2.A902)Dl.Ubi} P{UAS(FRT.y⁺CD2.A902)Dl.ΔC.MYC} P{UAS(-FRT)Dl.HRP} P{UAS(-FRT)Dl.LDL.MYC} P{UAS(-FRT)Dl.LDLm.MYC} P{UAS(-FRT)Dl.R.MYC} P{UAS(-FRT)Dl.Rm.MYC} P{UAS(-FRT)Dl.T:Hsap\MYC} P{UAS(FRT)-Dl.ubi.m} P{UAS(-FRT)Dl.ubi.m} P{UAS(-FRT)Dl.Ubi.MYC} P{UAS(-FRT)Dl.ΔC.MYC} P{UAS(-FRT)dpp.N} P{UAS-fng.K} P{UAS-GFP.T:Myc.T:nls2} P{UAS-hh.F.HA} P{UAS-mCD8::GFP.L} P{UAS-neur.L} P{UAS-Ser.mg5603} P{UAS-wg.flu} P{vg(D/V)-lacZ}
Genes (21)
	Avic\GFP bi ci ct Dl dpp Ecol\lacZ fng hh Hrs lqf Mmus\Cd8a neur Scer\GAL4 Scer\GAL80 Ser T:Arus\HRP T:Hsap\LDLR T:Hsap\MYC T:Hsap\Ubiquitin wg
Insertions (4)
	P{GawB}C-765 P{GawB}nubbin-AC-62 P{lacW}bi^X35 P{PZ}Dl⁰⁵¹⁵¹
Natural transposons (1)
	P-element