Localization and Activation of the Drosophila Protease Easter Require the ER-Resident Saposin-like Protein Seele
Localization and Activation of the Drosophila Protease Easter Require the ER-Resident Saposin-like Protein Seele
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DOI：
10.1016/j.cub.2010.09.069
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发表时间：
2010-11-09
期刊：
影响因子：
9.2
通讯作者：
Moussian, Bernard
中科院分区：
文献类型：
--
作者：
Stein, David;Charatsi, Iphigenie;Moussian, Bernard
果蝇胚胎背腹极性是由卵周空间中的一系列丝氨酸蛋白酶加工事件产生的。原肠胚形成缺陷会加工 Snake，然后将 Easter 裂解，然后将 Spatz le 加工成 Toll 受体的激活配体 [1-3]。 seele是在突变筛选中发现的，当卵巢种系克隆中纯合时，会导致形成具有改变的胚胎模式的子代胚胎；母体 seele 功能丧失会导致产生中度背侧化的胚胎 [4]。通过将原肠胚形成缺陷、Snake、Easter 和 Spatz le 的组成型活性版本与 seele 的功能丧失等位基因相结合，我们发现 Seele 活性对于 Spatz le 介导的 Toll 激活是可有可无的，但对于 Easter、Snake 和 Spatz le 发挥其对背腹模式的影响是必需的。此外，See le功能对于Easter从发育中的胚胎分泌到卵周空间以及Easter处理是特别需要的。 Seele 蛋白存在于胚盘胚胎的内质网中，表明其在将 Easter 运输到卵周空间中发挥作用，这是其加工和功能的先决条件。 Easter 向卵周空间的运输代表了控制果蝇胚胎背腹极性的信号转导途径中以前未被认识到的控制点。
Drosophila embryonic dorsal-ventral polarity is generated by a series of serine protease processing events in the egg perivitelline space. Gastrulation Defective processes Snake, which then cleaves Easter, which then processes Spatz le into the activating ligand for the Toll receptor [1-3]. seele was identified in a screen for mutations that, when homozygous in ovarian germline clones, lead to the formation of progeny embryos with altered embryonic patterning; maternal loss of seele function leads to the production of moderately dorsalized embryos [4]. By combining constitutively active versions of Gastrulation Defective, Snake, Easter, and Spatz le with loss-of-function alleles of seele, we find that See le activity is dispensable for Spatz le-mediated activation of Toll but is required for Easter, Snake, and Gastrulation Defective to exert their effects on dorsal-ventral patterning. Moreover, See le function is required specifically for secretion of Easter from the developing embryo into the perivitelline space and for Easter processing. Seele protein resides in the endoplasmic reticulum of blastoderm embryos, suggesting a role in the trafficking of Easter to the perivitelline space, prerequisite to its processing and function. Easter transport to the perivitelline space represents a previously unappreciated control point in the signal transduction pathway that controls Drosophila embryonic dorsal-ventral polarity.