title: Identification of a tetrameric hedgehog signaling complex.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0524, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Stegman
authors.forename: J E
authors.initials: JE
authors.lastname: Vallance
authors.forename: G
authors.initials: G
authors.lastname: Elangovan
authors.forename: J
authors.initials: J
authors.lastname: Sosinski
authors.forename: Y
authors.initials: Y
authors.lastname: Cheng
authors.forename: D J
authors.initials: DJ
authors.lastname: Robbins
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D019281:Dimerization; D004330:Drosophila; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins / Q000737:chemistry / Q000502:physiology; D016547:Kinesins / Q000737:chemistry / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins; D014157:Transcription Factors; C092937:ci protein, Drosophila; C107452:cos protein, Drosophila; C077245:hh protein, Drosophila; C085770:fu protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins