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

Science  14 Sep 2001:
Vol. 293, Issue 5537, pp. 2080-2084
DOI: 10.1126/science.1064437

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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. Theski gene encodes an apparent acyltransferase, and we provide genetic and biochemical evidence that Hh proteins from skimutant cells retain carboxyl-terminal cholesterol modification but lack amino-terminal palmitate modification. Our results suggest thatski 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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: pbeachy{at} (P.A.B.), basler{at} (K.B.)

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