Regulated endocytic routing modulates wingless signaling in Drosophila embryos.
Embryos have evolved various strategies to confine the action of secreted signals. Using an HRP-Wingless fusion protein to track the fate of endocytosed Wingless, we show that degradation by targeting to lysosomes is one such strategy. Wingless protein is specifically degraded at the posterior of each stripe of wingless transcription, even under conditions of overexpression. If lysosomal degradation is compromised genetically or chemically, excess Wingless accumulates and ectopic signaling ensues. In the wild-type, Wingless degradation is slower at the anterior than at the posterior. This follows in part from the segmental activation of signaling by the epidermal growth factor receptor, which accelerates Wingless degradation at the posterior, thus leading to asymmetrical Wingless signaling along the anterior-posterior axis.
Dubois
L
L
National Institute for Medical Research, The Ridgeway, Mill Hill, NW7 1AA London, United Kingdom.
Lecourtois
M
M
Alexandre
C
C
Hirst
E
E
Vincent
J P
JP
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D002966:Clathrin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D051157:Frizzled Receptors; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014157:Transcription Factors; D051155:Wnt1 Protein
D000962:Antimalarials; D002966:Clathrin; D004268:DNA-Binding Proteins; C104790:DOR protein, Drosophila; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C106185:engrailed homeobox proteins; C058784:fz protein, Drosophila; C101703:fz2 protein, Drosophila; C074622:wg protein, Drosophila; D002738:Chloroquine; D006735:Horseradish Peroxidase