Skinny Hedgehog, an Acyltransferase Required for Palmitoylation and Activity of the Hedgehog Signal

• Published in: Science (American Association for the Advancement of Science) Vol. 293; no. 5537; pp. 2080 - 2084
• Main Authors: Chamoun, Zeina, Mann, Randall K., Nellen, Denise, von Kessler, Doris P., Bellotto, Manolo, Beachy, Philip A., Basler, Konrad
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 14-09-2001; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Acylation; acyltransferase; Acyltransferases - chemistry; Acyltransferases - genetics; Acyltransferases - metabolism; Alleles; Amino Acid Sequence; Amino Acid Substitution; Animals; Biochemistry; Biological and medical sciences; Body Patterning; Cell lines; Cholesterol - metabolism; Cholesterols; Cultured cells; Drosophila; Drosophila melanogaster; Drosophila melanogaster - embryology; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila Proteins; Embryos; Evidence; Fundamental and applied biological sciences. Psychology; Gene Expression; Genes; Genes, Insect; Genetics; Hedgehog (Hh) protein; Hedgehog Proteins; Insect Proteins - chemistry; Insect Proteins - genetics; Insect Proteins - metabolism; Insects; Larvae; Molecular and cellular biology; Molecular biology; Molecular Sequence Data; Mutation; Palmitates; palmitic acid; Palmitic Acid - metabolism; palmitoylation; Protein Structure, Tertiary; Proteins; Signal Transduction; skinny hedgehog (ski) gene; Skis; Transcripts (Written Records); Transgenes
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1064437

One of the most dominant influences in the patterning of multicellular embryos is exerted by the Hedgehog (Hh) family of secreted signaling proteins. Here, we identify a segment polarity gene in Drosophila melanogaster, skinny hedgehog (ski), and show that its product is required in Hh-expressing cells for production of appropriate signaling activity in embryos and in the imaginal precursors of adult tissues. The ski gene encodes an apparent acyltransferase, and we provide genetic and biochemical evidence that Hh proteins from ski mutant cells retain carboxyl-terminal cholesterol modification but lack amino-terminal palmitate modification. Our results suggest that ski encodes an enzyme that acts within the secretory pathway to catalyze amino-terminal palmitoylation of Hh, and further demonstrate that this lipid modification is required for the embryonic and larval patterning activities of the Hh signal.