Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing.
During animal development, Wnt/Wingless (Wg) signaling is required for the patterning of multiple tissues. While insufficient signal transduction is detrimental to normal development, ectopic activation of the pathway can be just as devastating. Thus, numerous controls exist to precisely regulate Wg signaling levels. Endocytic trafficking of pathway components has recently been proposed as one such control mechanism. Here, we characterize the vesicular trafficking of Wg and its receptors, Arrow and DFrizzled-2 (DFz2), and investigate whether trafficking is important to regulate Wg signaling during dorsoventral patterning of the larval wing. We demonstrate a role for Arrow and DFz2 in Wg internalization. Subsequently, Wg, Arrow and DFz2 are trafficked through the endocytic pathway to the lysosome, where they are degraded in a hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-dependent manner. Surprisingly, we find that Wg signaling is not attenuated by lysosomal targeting in the wing disc. Rather, we suggest that signaling is dampened intracellularly at an earlier trafficking step. This is in contrast to patterning of the embryonic epidermis, where lysosomal targeting is required to restrict the range of Wg signaling. Thus, signal modulation by endocytic routing will depend on the tissue to be patterned and the goals during that patterning event.
Rives
Anna F
AF
University of Pennsylvania School of Medicine, Department of Cell and Developmental Biology, Philadelphia, PA 190104-6058, USA.
Rochlin
Kate M
KM
Wehrli
Marcel
M
Schwartz
Stephanie L
SL
DiNardo
Stephen
S
D000818:Animals; D004330:Drosophila / Q000254:growth & development*; D029721:Drosophila Proteins / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport; D051157:Frizzled Receptors / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D010750:Phosphoproteins / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014921:Wings, Animal / Q000254:growth & development*; D051155:Wnt1 Protein
D029721:Drosophila Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D051157:Frizzled Receptors; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D051155:Wnt1 Protein; C474373:arr protein, Drosophila; C101703:fz2 protein, Drosophila; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; C074622:wg protein, Drosophila