Bickel Daniela, Shah Ripal, Gesualdi Scott C, Haerry Theodor E
Department of Biological Sciences, Center for Molecular Biology and Biotechnology, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA.
Mech Dev. 2008 Jan-Feb;125(1-2):117-29. doi: 10.1016/j.mod.2007.09.013. Epub 2007 Oct 5.
Follistatin (FS) is one of several secreted proteins that modulate the activity of TGF-beta family members during development. The structural and functional analysis of Drosophila Follistatin (dFS) reveals important differences between dFS and its vertebrate orthologues: it is larger, more positively charged, and proteolytically processed. dFS primarily inhibits signaling of Drosophila Activin (dACT) but can also inhibit other ligands like Decapentaplegic (DPP). In contrast, the presence of dFS enhances signaling of the Activin-like protein Dawdle (DAW), indicating that dFS exhibits a dual function in promoting and inhibiting signaling of TGF-beta ligands. In addition, FS proteins may also function in facilitating ligand diffusion. We find that mutants of daw are rescued in significant numbers by expression of vertebrate FS proteins. Since two PiggyBac insertions in dfs are not lethal, it appears that the function of dFS is non-essential or functionally redundant.
卵泡抑素(FS)是在发育过程中调节转化生长因子-β(TGF-β)家族成员活性的几种分泌蛋白之一。对果蝇卵泡抑素(dFS)的结构和功能分析揭示了dFS与其脊椎动物直系同源物之间的重要差异:它更大、带更多正电荷且经过蛋白水解加工。dFS主要抑制果蝇激活素(dACT)的信号传导,但也能抑制其他配体,如Decapentaplegic(DPP)。相比之下,dFS的存在增强了激活素样蛋白Dawdle(DAW)的信号传导,表明dFS在促进和抑制TGF-β配体的信号传导中具有双重功能。此外,FS蛋白也可能在促进配体扩散中发挥作用。我们发现,通过表达脊椎动物FS蛋白,大量daw突变体得到了拯救。由于dfs中的两个PiggyBac插入并不致命,看来dFS的功能是非必需的或在功能上是冗余的。