Drosophila KDEL receptor function in the embryonic salivary gland and epidermis.

Drosophila KDEL receptor function in the embryonic salivary gland and epidermis.
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DOI:
10.1371/journal.pone.0077618
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Andrew DJ
Andrew DJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Abrams EW;Cheng YL;Andrew DJ

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分泌途径的核心成分已在单细胞系统中大量鉴定和研究,如芽殖酵母S。酿酒酵母或哺乳动物组织培养物中。这些研究提供了分泌机制的分子功能的细节,但是,他们未能提供深入了解这些蛋白质在高等真核生物的专门器官的背景下的作用。在这里,我们确定和表征的第一个失去功能的突变KDEL受体基因从高等真核生物。果蝇KDEL受体基因KdelR(以前称为dmErd2)的转录本由母体提供,在后期阶段,在几种胚胎细胞类型中的水平升高,包括唾液腺分泌细胞,脂肪体和表皮。我们发现,与酿酒酵母Erd2突变体,这是可行的,KdelR突变是早期幼虫致死,与纯合子突变动物死亡的第一龄幼虫。KdelR突变体的幼虫角质层缺陷与观察到的其他核心分泌途径基因的功能丧失突变和CrebA突变相似,CrebA编码一种bZip转录因子,在专门的分泌细胞类型中协同上调分泌途径组分基因。使用唾液腺,我们证明了KdelR在维持可溶性常驻ER蛋白的一个子集的ER池的要求。这些研究强调了果蝇唾液腺作为研究复杂真核生物体内分泌途径分子机制的独特系统的实用性。
Core components of the secretory pathway have largely been identified and studied in single cell systems such as the budding yeast S. cerevisiae or in mammalian tissue culture. These studies provide details on the molecular functions of the secretory machinery; they fail, however, to provide insight into the role of these proteins in the context of specialized organs of higher eukaryotes. Here, we identify and characterize the first loss-of-function mutations in a KDEL receptor gene from higher eukaryotes. Transcripts from the Drosophila KDEL receptor gene KdelR – formerly known as dmErd2 – are provided maternally and, at later stages, are at elevated levels in several embryonic cell types, including the salivary gland secretory cells, the fat body and the epidermis. We show that, unlike Saccharomyces cerevisiae Erd2 mutants, which are viable, KdelR mutations are early larval lethal, with homozygous mutant animals dying as first instar larvae. KdelR mutants have larval cuticle defects similar to those observed with loss-of-function mutations in other core secretory pathway genes and with mutations in CrebA, which encodes a bZip transcription factor that coordinately upregulates secretory pathway component genes in specialized secretory cell types. Using the salivary gland, we demonstrate a requirement for KdelR in maintaining the ER pool of a subset of soluble resident ER proteins. These studies underscore the utility of the Drosophila salivary gland as a unique system for studying the molecular machinery of the secretory pathway in vivo in a complex eukaryote.
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