Biochemical defects of mutant nudel alleles causing early developmental arrest or dorsalization of the Drosophila embryo.
Biochemical defects of mutant nudel alleles causing early developmental arrest or dorsalization of the Drosophila embryo.
复制标题
突变核等位基因的生化缺陷导致果蝇胚胎早期发育停滞或背侧化。
DOI：
10.1093/genetics/154.1.247
复制
发表时间：
2000
期刊：
影响因子：
3.3
通讯作者：
Hashimoto,C
中科院分区：
文献类型：
--
作者：
LeMosy,EK;Leclerc,CL;Hashimoto,C
果蝇的nudel基因对于卵的结构完整性和胚胎的背腹图案都是母性所需的。它编码一种由卵泡细胞分泌的结构模块蛋白。遗传和分子研究表明，Nudel蛋白在功能上也是模块化的，具有腹侧发育特别需要的丝氨酸蛋白酶结构域。在这里，我们描述了生化和免疫定位研究，提供洞察裸突变产生的不同表型和这些等位基因之间的相互作用的分子基础。导致胚胎背腹极性丧失的突变导致Nudel蛋白酶结构域激活失败。我们的分析支持以前的研究结果，即蛋白酶结构域的催化活性是必需的背腹图案和Nudel蛋白酶是自动激活的，并揭示了一个重要的作用，在Nudel蛋白酶功能的蛋白酶结构域附近的区域。导致卵子脆性和早期胚胎停滞的突变导致细胞外Nudel蛋白的显著减少，这是由于翻译后加工、稳定性或分泌的缺陷。在这些和其他丝氨酸蛋白酶的研究的基础上，我们提出了裸等位基因之间的互补和拮抗相互作用的潜在机制。
The nudel gene of Drosophila is maternally required both for structural integrity of the egg and for dorsoventral patterning of the embryo. It encodes a structurally modular protein that is secreted by ovarian follicle cells. Genetic and molecular studies have suggested that the Nudel protein is also functionally modular, with a serine protease domain that is specifically required for ventral development. Here we describe biochemical and immunolocalization studies that provide insight into the molecular basis for the distinct phenotypes produced by nudel mutations and for the interactions between these alleles. Mutations causing loss of embryonic dorsoventral polarity result in a failure to activate the protease domain of Nudel. Our analyses support previous findings that catalytic activity of the protease domain is required for dorsoventral patterning and that the Nudel protease is auto-activated and reveal an important role for a region adjacent to the protease domain in Nudel protease function. Mutations causing egg fragility and early embryonic arrest result in a significant decrease in extracellular Nudel protein, due to defects in post-translational processing, stability, or secretion. On the basis of these and other studies of serine proteases, we suggest potential mechanisms for the complementary and antagonistic interactions between the nudel alleles.