Rasp, a putative transmembrane acyltransferase, is required for Hedgehog signaling.
Members of the Hedgehog (Hh) family encode secreted molecules that act as potent organizers during vertebrate and invertebrate development. Post-translational modification regulates both the range and efficacy of Hh protein. One such modification is the acylation of the N-terminal cysteine of Hh. In a screen for zygotic lethal mutations associated with maternal effects, we have identified rasp, a novel Drosophila segment polarity gene. Analysis of the rasp mutant phenotype, in both the embryo and wing imaginal disc demonstrates that rasp does not disrupt Wnt/Wingless signaling but is specifically required for Hh signaling. The requirement of rasp is restricted only to those cells that produce Hh; hh transcription, protein levels and distribution are not affected by the loss of rasp. Molecular analysis reveals that rasp encodes a multipass transmembrane protein that has homology to a family of membrane bound O-acyl transferases. Our results suggest that Rasp-dependent acylation is necessary to generate a fully active Hh protein.
Micchelli
Craig A
CA
Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. cmicchel@genetics.med.harvard.edu
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Inge
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Selva
Erica
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Mogila
Vladic
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Perrimon
Norbert
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D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism; D053823:Hedgehog Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D051155:Wnt1 Protein
D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051155:Wnt1 Protein; C446031:rasp protein, Drosophila; C074622:wg protein, Drosophila; C077245:hh protein, Drosophila; D000217:Acyltransferases