Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified hedgehog from signaling cells.
Members of the Hedgehog (Hh) family of secreted signaling proteins function as potent short-range organizers in animal development. Their range of action is limited by a C-terminal cholesterol tether and the upregulation of Patched (Ptc) receptor levels. Here we identify a novel segment-polarity gene in Drosophila, dispatched (disp), and demonstrate that its product is required in sending cells for normal Hh function. In the absence of Disp, cholesterol-modified but not cholesterol-free Hh is retained in these cells, indicating that Disp functions to release cholesterol-anchored Hh. Despite their opposite roles, Disp and Ptc share structural homology in the form of a sterol-sensing domain, suggesting that release and sequestration of cholesterol-modified Hh may be based on related molecular pathways.
Burke
R
R
Institut für Molekularbiologie, Universität Zürich, Switzerland.
Nellen
D
D
Bellotto
M
M
Hafen
E
E
Senti
K A
KA
Dickson
B J
BJ
Basler
K
K
D000595:Amino Acid Sequence; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D003001:Cloning, Molecular; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007814:Larva; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D019076:Transgenes
D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; C403224:disp protein, Drosophila; C070844:ptc protein, Drosophila; C077245:hh protein, Drosophila; D002784:Cholesterol