Arrow (LRP6) and Frizzled2 cooperate to degrade Wingless in Drosophila imaginal discs.
Lysosome-mediated ligand degradation is known to shape morphogen gradients and modulate the activity of various signalling pathways. We have investigated the degradation of Wingless, a Drosophila member of the Wnt family of secreted growth factors. We find that one of its signalling receptors, Frizzled2, stimulates Wingless internalization both in wing imaginal discs and cultured cells. However, this is not sufficient for degradation. Indeed, as shown previously, overexpression of Frizzled2 leads to Wingless stabilization in wing imaginal discs. We show that Arrow (the Drosophila homologue of LRP5/6), another receptor involved in signal transduction, abrogates such stabilization. We provide evidence that Arrow stimulates the targeting of Frizzled2-Wingless (but not Dally-like-Wingless) complexes to a degradative compartment. Thus, Frizzled2 alone cannot lead Wingless all the way from the plasma membrane to a degradative compartment. Overall, Frizzled2 achieves ligand capture and internalization, whereas Arrow, and perhaps downstream signalling, are essential for lysosomal targeting.
Piddini
Eugenia
E
National Institute for Medical Research, The Ridgeway Mill Hill, London NW7 1AA, UK.
Marshall
Francis
F
Dubois
Laurence
L
Hirst
Elizabeth
E
Vincent
Jean-Paul
JP
D000818:Animals; D002478:Cells, Cultured; D004330:Drosophila / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology; D051157:Frizzled Receptors / Q000502:physiology*; D007814:Larva / Q000378:metabolism / Q000502:physiology; D008247:Lysosomes / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction; D051155:Wnt1 Protein
D029721:Drosophila Proteins; D051157:Frizzled Receptors; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D051155:Wnt1 Protein; C474373:arr protein, Drosophila; C101703:fz2 protein, Drosophila; C074622:wg protein, Drosophila