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J. Biol. Chem., Vol. 275, Issue 29, 21809-21812, July 21, 2000
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From the Department of Molecular Genetics, Biochemistry and
Microbiology, University of Cincinnati College of Medicine, Cincinnati,
Ohio 45267-0524 and § G. W. Hooper Foundation, University
of California, San Francisco, San Francisco, California 94143-0552
Hedgehog (Hh) signal transduction requires a
large cytoplasmic multi-protein complex that binds microtubules in an
Hh-dependent manner. Here, we show that three members of
this complex, Costal2 (Cos2), Fused (Fu), and Cubitus interruptus
(Ci), bind each other directly to form a trimeric complex. We
demonstrate that this trimeric signaling complex exists in
Drosophila lacking Suppressor of Fused (Su(fu)), an
extragenic suppressor of fu, indicating that Su(fu) is not
required for the formation, or apparently function, of the Hh signaling
complex. However, we subsequently show that Su(fu), although not
a requisite component of this complex, does form a tetrameric complex
with Fu, Cos2, and Ci. This additional Su(fu)-containing Hh signaling
complex does not appear to be enriched on microtubules.
Additionally, we demonstrate that in response to Hh Ci accumulates in
the nucleus without its various cytoplasmic binding partners, including
Su(fu). We discuss a model in which Su(fu) and Cos2 each bind to Fu and
Ci to exert some redundant effect on Ci such as cytoplasmic retention.
This model is consistent with genetic data demonstrating that Su(fu) is
not required for Hh signal transduction proper and with the elaborate
genetic interactions observed among Su(fu), fu,
cos2, and ci.
ACCELERATED PUBLICATION
Identification of a Tetrameric Hedgehog Signaling Complex*
,,
*
This work was supported by Grant CA82628-01 from the
National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
These authors contributed equally to this paper.
¶
Recipient of a Burroughs Wellcome Fund Career Award in the
Biomedical Sciences. To whom correspondence should be addressed: 231 Bethesda Ave., Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH
45267-0524. Tel.: 513-558-6742; Fax: 513-558-8474; E-mail:
david. robbins{at}uc.edu.
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