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Published Online August 2, 2001
Science DOI: 10.1126/science.1064437

Reports

Submitted on July 16, 2001
Accepted on July 24, 2001

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

Zeina Chamoun 1, Randall K. Mann 2, Denise Nellen 1, Doris P. von Kessler 2, Manolo Bellotto 1, Philip A. Beachy 2*, Konrad Basler 1*

1 Institut für Molekularbiologie and Zoologisches Institut, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
2 Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

* To whom correspondence should be addressed. E-mail: basler{at}molbio.unizh.ch.

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, 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 COOH-terminal cholesterol modification but lack NH2-terminal palmitate modification. Our results suggest that ski encodes an enzyme that acts within the secretory pathway to catalyze NH2-terminal palmitoylation of Hh, and they further demonstrate that this lipid modification is required for the embryonic and larval patterning activities of the Hh signal.


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