Sulfation of eggshell components by Pipe defines dorsal-ventral polarity in the Drosophila embryo.

Sulfation of eggshell components by Pipe defines dorsal-ventral polarity in the Drosophila embryo.
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DOI:
10.1016/j.cub.2009.05.050
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发表时间:
2009-07-28
期刊:
Current biology : CB
影响因子:
--
通讯作者:
Stein D
Stein D
中科院分区:
其他
文献类型:
--
作者:
Zhang Z;Stevens LM;Stein D

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果蝇胚胎背腹侧(DV)极性是由一组顺序作用的丝氨酸蛋白酶控制的,这些丝氨酸蛋白酶位于胚胎膜和蛋壳之间充满液体的卵黄周围空间,它们为胚胎腹侧的Toll受体产生配体。蛋白酶级联的空间控制依赖于管道硫转移酶,这是一种脊椎动物糖胺聚糖修饰酶的苍蝇同源物,在发育中的卵母细胞周围滤泡上皮的腹侧细胞中表达。Pipe酶靶点的鉴定仍然是我们对卵泡周围蛋白酶级联控制机制的理解的主要空白,因此胚胎DV模式。在这里,我们发现卵黄膜样蛋白(VML)经历了管道依赖的硫酸化,并且与从卵腔向胚胎传递位置信息的作用一致,在与卵泡细胞的位置相对应的位置被合并到蛋壳中。卵泡细胞是从卵泡细胞分泌的。虽然VML在致敏遗传背景下影响胚胎DV模式,但VML对DV轴的形成并不是必需的,这表明在Pipe酶靶点的组成中存在冗余。相应地,我们发现卵黄膜的附加结构组分经历管道依赖的硫酸酸化。在确定Pipe难以捉摸的靶点时,这项工作指出卵黄膜是产生果蝇DV轴的信号来源,并为理解在胚胎模式形成过程中控制丝氨酸蛋白酶活性的空间特异性激活的机制提供了一个框架。
Drosophila embryonic dorsal-ventral (DV) polarity is controlled by a group of sequentially acting serine proteases located in the fluid-filled perivitelline space between the embryonic membrane and the eggshell, which generate the ligand for the Toll receptor on the ventral side of the embryo. Spatial control of the protease cascade relies on the Pipe sulfotransferase, a fly homologue of vertebrate glycosaminoglycan modifying enzymes, which is expressed in ventral cells of the follicular epithelium surrounding the developing oocyte. The identification of the Pipe enzymatic target has remained a major gap in our understanding of the mechanism controlling the perivitelline protease cascade, and hence embryonic DV patterning. Here we show that the protein Vitelline Membrane-Like (VML) undergoes Pipe-dependent sulfation and, consistent with a role in conveying positional information from the egg chamber to the embryo, becomes incorporated into the eggshell at a position corresponding to the location of the follicle cells from which it was secreted. Although VML influences embryonic DV pattern in a sensitized genetic background, VML is not essential for DV axis formation, suggesting that there is redundancy in the composition of the Pipe enzymatic target. Correspondingly, we find that additional structural components of the vitelline membrane undergo Pipe-dependent sulfation. In identifying the elusive targets of Pipe, this ork points to the vitelline membrane as the source of signals that generate the Drosophila DV axis and provides a framework for understanding the mechanism controlling spatially-specific activation of serine protease activity during embryonic pattern formation.
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