Stein David, Cho Yong Suk, Zhang Zhenyu, Stevens Leslie M
Section of Molecular Cell and Developmental Biology and Institute for Cellular and Molecular Biology; University of Texas at Austin; Austin, Texas, USA.
Fly (Austin). 2008 Jul-Aug;2(4):220-8. doi: 10.4161/fly.6794.
Drosophila embryonic dorsal-ventral polarity is defined by a maternally encoded signal transduction pathway. Gastrulation Defective, Snake, and Easter comprise a serine protease cascade that operates in the perivitelline space to generate active ligand for the Toll receptor, which resides in the embryonic membrane. Toll is activated only on the ventral side of the embryo. Spatial regulation of this pathway is initiated by the ventrally restricted expression of the sulfotransferase Pipe in the follicular epithelium that surrounds the developing oocyte. Pipe is thought to modify a target molecule that is secreted and localized within the ventral region of the egg and future embryo, where it influences the activity of the pathway such that active Toll ligand is produced only ventrally. A potential substrate for Pipe is encoded by nudel, which is expressed throughout the follicle cell layer and encodes a large, multi-functional secreted protein that contains a serine protease domain as well as other structural features characteristic of extracellular matrix proteins. A previous mosaic analysis suggested that the protease domain of Nudel is not a target for Pipe activity as its expression is not required in pipe-expressing cells, but failed to rule out such a role for other functional domains of the protein. To investigate this possibility, we carried out a mosaic analysis of additional nudel alleles, including some that affect the entire protein. Our analysis demonstrated that proteolytically processed segments of Nudel are secreted into the perivitelline space and stably localized, as would be expected for the target of Pipe, However, we found no requirement for nudel to be expressed in ventral, pipe-expressing follicle cells, thereby eliminating Nudel as an essential substrate of Pipe sulfotransferase activity.
果蝇胚胎的背腹极性由母体编码的信号转导途径决定。原肠胚形成缺陷蛋白、蛇蛋白和复活节蛋白构成了一个丝氨酸蛋白酶级联反应,该反应在卵黄周隙中起作用,为位于胚胎膜上的Toll受体生成活性配体。Toll仅在胚胎的腹侧被激活。该信号通路的空间调控始于包围发育中卵母细胞的卵泡上皮中腹侧受限表达的磺基转移酶Pipe。Pipe被认为会修饰一种分泌并定位于卵子和未来胚胎腹侧区域的靶分子,在该区域它会影响信号通路的活性,从而仅在腹侧产生活性Toll配体。Pipe的一个潜在底物由nudel编码,nudel在整个卵泡细胞层中表达,编码一种大型多功能分泌蛋白,该蛋白包含一个丝氨酸蛋白酶结构域以及细胞外基质蛋白特有的其他结构特征。先前的嵌合分析表明,Nudel的蛋白酶结构域不是Pipe活性的靶标,因为在表达Pipe的细胞中不需要其表达,但未能排除该蛋白其他功能结构域的这种作用。为了研究这种可能性,我们对其他nudel等位基因进行了嵌合分析,包括一些影响整个蛋白的等位基因。我们的分析表明,Nudel经蛋白水解处理的片段会分泌到卵黄周隙中并稳定定位,这与Pipe的靶标预期情况相符。然而,我们发现腹侧表达Pipe的卵泡细胞中不需要表达nudel,从而排除了Nudel作为Pipe磺基转移酶活性的必需底物的可能性。