Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail.
The Hedgehog (Hh) family of secreted proteins controls many aspects of growth and patterning in animal development. The seven-transmembrane protein Smoothened (Smo) transduces the Hh signal in both vertebrates and invertebrates; however, the mechanism of its action remains unknown. We found that Smo lacking its C-terminal tail (C-tail) is inactive, whereas membrane-tethered Smo C-tail has constitutive albeit low levels of Hh signaling activity. Smo physically interacts with Costal2 (Cos2) and Fused (Fu) through its C-tail. Deletion of the Cos2/Fu-binding domain from Smo abolishes its signaling activity. Moreover, overexpressing Cos2 mutants that fail to bind Fu and Ci but retain Smo-binding activity blocks Hh signaling. Taken together, our results suggest that Smo transduces the Hh signal by physically interacting with the Cos2/Fu protein complex.
Jia
Jianhang
J
Center for Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133, USA. jin.jiang@utsouthwestern.edu
Tong
Chao
C
Jiang
Jin
J
D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins / Q000378:metabolism*; D053823:Hedgehog Proteins; D016547:Kinesins / Q000378:metabolism*; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D015398:Signal Transduction / Q000502:physiology; D000072086:Smoothened Receptor
D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; C107452:cos protein, Drosophila; C100664:smo protein, Drosophila; C077245:hh protein, Drosophila; C085770:fu protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins