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 Basler1
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.
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.
*
These authors contributed equally to this work.
To whom correspondence should be addressed.
E-mail: pbeachy{at}jhmi.edu (P.A.B.),
basler{at}molbio.unizh.ch (K.B.)
