Accelerated publication - Identification of a tetrameric hedgehog signaling complex

Hedgehog (Hh) signal transduction requires a large cytoplasmic multi-protei n complex that binds microtubules in an Hh-dependent manner. Here, we show that three members of this complex, Costal2 (Cosa), 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 lacki ng 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), althou gh not a requisite component of this complex, does form a tetrameric comple x with Fu, Cos2, and Ci. This additional Su(fu)-containing Hh signaling com plex does not appear to be enriched on microtubules, Additionally, we demon strate that in response to Hh Ci accumulates in the nucleus without its var ious cytoplasmic binding partners, including Su(fu), We discuss a model in which Su(fu) and Cosa 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), f u, cos2, and ci.