Lipoprotein-heparan sulfate interactions in the Hh pathway.
The Drosophila lipoprotein particle, Lipophorin, bears lipid-linked morphogens on its surface and is required for long-range signaling activity of Wingless and Hedgehog. Heparan sulfate proteoglycans are also critical for trafficking and signaling of these morphogens. Here we show that Lipophorin interacts with the heparan sulfate moieties of the glypicans Dally and Dally-like. Membrane-associated glypicans can recruit Lipophorin to disc tissue, and remain associated with these particles after they are released from the membrane by cleavage of their gpi anchors. The released form of Dally colocalizes with Patched, Hedgehog, and Lipophorin in endosomes and increases Hedgehog signaling efficiency without affecting its distribution. These data suggest that heparan sulfate proteoglycans may influence lipid-linked morphogen signaling, at least in part, by binding to Lipophorin. They further suggest that the complement of proteins present on lipoprotein particles can regulate the activity of morphogens.
Eugster
Christina
C
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse-108, 01307 Dresden, Germany.
Panáková
Daniela
D
Mahmoud
Ali
A
Eaton
Suzanne
S
D000818:Animals; D016764:Cell Polarity / Q000502:physiology; D004330:Drosophila / Q000235:genetics / Q000254:growth & development*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D053673:Glypicans / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D053823:Hedgehog Proteins / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D021381:Protein Transport / Q000502:physiology*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014921:Wings, Animal / Q000254:growth & development / Q000502:physiology; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
D029721:Drosophila Proteins; D017261:Glycosylphosphatidylinositols; D053673:Glypicans; D049452:Green Fluorescent Proteins; D053823:Hedgehog Proteins; D006497:Heparan Sulfate; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D020696:rab5 GTP-Binding Proteins; C098128:dally protein, Drosophila; C032830:lipophorin; C077245:hh protein, Drosophila