Stegman M A, Vallance J E, Elangovan G, Sosinski J, Cheng Y, Robbins D J
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0524, USA.
J Biol Chem. 2000 Jul 21;275(29):21809-12. doi: 10.1074/jbc.C000043200.
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.
刺猬信号通路（Hh）的信号转导需要一个大型的细胞质多蛋白复合物，该复合物以Hh依赖的方式结合微管。在此，我们表明该复合物的三个成员，Costal2（Cos2）、Fused（Fu）和Cubitus interruptus（Ci），直接相互结合形成一个三聚体复合物。我们证明，在缺乏Fused抑制因子（Su(fu)）的果蝇中存在这种三聚体信号复合物，Su(fu)是fu的一个基因外抑制因子，这表明Su(fu)对于Hh信号复合物的形成或明显的功能并非必需。然而，我们随后表明，Su(fu)虽然不是该复合物的必需成分，但确实与Fu、Cos2和Ci形成一个四聚体复合物。这种额外的含Su(fu)的Hh信号复合物似乎没有在微管上富集。此外，我们证明，在Hh信号的作用下，Ci在没有其各种细胞质结合伙伴（包括Su(fu)）的情况下在细胞核中积累。我们讨论了一个模型，其中Su(fu)和Cos2各自与Fu和Ci结合，对Ci发挥一些冗余作用，如细胞质滞留。该模型与遗传数据一致，这些数据表明Su(fu)对于正常的Hh信号转导并非必需，并且与在Su(fu)、fu、cos2和ci之间观察到的复杂遗传相互作用一致。
