Cellular trafficking of the glypican Dally-like is required for full-strength Hedgehog signaling and wingless transcytosis.
Hedgehog (Hh) and Wingless (Wg) morphogens specify cell fate in a concentration-dependent manner in the Drosophila wing imaginal disc. Proteoglycans, components of the extracellular matrix, are involved in Hh and Wg stability, spreading, and reception. In this study, we demonstrate that the glycosyl-phosphatidyl-inositol (GPI) anchor of the glypican Dally-like (Dlp) is required for its apical internalization and its subsequent targeting to the basolateral compartment of the epithelium. Dlp endocytosis from the apical surface of Hh-receiving cells catalyzes the internalization of Hh bound to its receptor Patched (Ptc). The cointernalization of Dlp with the Hh/Ptc complex is dynamin dependent and necessary for full-strength Hh signaling. We also demonstrate that Wg is secreted apically in the disc epithelium and that apicobasal trafficking of Dlp allows Wg transcytosis to favor Wg spreading along the basolateral compartment. Thus, Dlp endocytosis is a common regulatory mechanism of both Hh and Wg morphogen action.
Gallet
Armel
A
Institut Biologie du Développement et Cancer-IBDC, Université de Nice Sophia-Antipolis, UMR 6543 CNRS, Centre de Biochimie, Parc Valrose, 06108 Nice cedex 2, France. gallet@unice.fr
Staccini-Lavenant
Laurence
L
Thérond
Pascal P
PP
D000818:Animals; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005799:Genes, Dominant; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D053673:Glypicans / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D000072079:Patched Receptors; D021381:Protein Transport; D011509:Proteoglycans / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013816:Thermodynamics; D014921:Wings, Animal / Q000166:cytology / Q000378:metabolism; D051155:Wnt1 Protein
D029721:Drosophila Proteins; D017261:Glycosylphosphatidylinositols; D053673:Glypicans; D053823:Hedgehog Proteins; D000072079:Patched Receptors; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D051155:Wnt1 Protein; C420997:dlp protein, Drosophila; C074622:wg protein, Drosophila