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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The Drosophila gene Start1: A putative cholesterol transporter and key regulator of ecdysteroid synthesis
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The Drosophila gene Start1: A putative cholesterol transporter and key regulator of ecdysteroid synthesis

机译:果蝇基因Start1:假定的胆固醇转运蛋白和蜕皮激素合成的关键调节剂

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摘要

Human metastatic lymph node 64 (MLN64) is a transmembrane protein that shares homology with the cholesterol-binding vertebrate steroid acute regulatory protein (StAR)-related lipid transfer domain (START) and is involved in cholesterol traffic and steroid synthesis. We identified a Drosophila melanogaster gene whose putative protein product shows extensive homology with MLN64 and that we name Start1 (FlyBase CG3522). The putative Start1 protein, derived from Start1 cDNA sequences, contains an additional 122 aa of unknown function within the StAR-related lipid transfer domain. Similar inserts seem to exist in the Start1 homo-logues of Drosophila pseudoobscura and Anopheles gambiae, but not in the homologous protein of the urochordate Ciona intesti-nalis. Immunostaining using an insert-specific antibody confirms the presence of the insert in the cytoplasm. Whereas RT-PCR data indicate that Start1 is expressed ubiquitously, RNA in situ hybridizations demonstrate its overexpression in prothoracic gland cells, where ecdysteroids are synthesized from cholesterol. Transcripts of Start1 are detectable in embryonic ring gland progenitor cells and are abundant in prothoracic glands of larvae showing wave-like expression during larval stages. In adults, Start1 is expressed in nurse cells of the ovary. These observations are consistent with the assumption that Start1 plays a key role in the regulation of ecdysteroid synthesis. Vice versa, the expression of Start1 itself seems to depend on ecdysone, as in the ecdysone-deficient mutant ecd-1. Start1 expression is severely reduced.
机译:人转移淋巴结64(MLN64)是一种跨膜蛋白,与胆固醇结合的脊椎动物类固醇急性调节蛋白(StAR)相关的脂质转移域(START)具有同源性,并参与胆固醇运输和类固醇合成。我们鉴定出果蝇的果蝇基因,其推定的蛋白质产物与MLN64具有广泛的同源性,我们将其命名为Start1(FlyBase CG3522)。推定的Start1蛋白衍生自Start1 cDNA序列,在StAR相关的脂质转移结构域内还包含122 aa未知功能。在果蝇假冈比亚和冈比亚按蚊的Start1同源物中似乎存在相似的插入片段,而在urochordate Ciona肠道的同源蛋白中则没有相似的插入片段。使用插入物特异性抗体的免疫染色证实了插入物在细胞质中的存在。尽管RT-PCR数据表明Start1普遍表达,但RNA原位杂交表明其在胸腺细胞中过表达,而蜕皮类固醇是由胆固醇合成的。在胚胎环腺祖细胞中可检测到Start1的转录本,并且在幼虫的胸腺中含量丰富,在幼虫阶段表现出波状表达。在成年人中,Start1在卵巢的护士细胞中表达。这些观察结果与Start1在蜕皮甾类合成的调节中起关键作用的假设是一致的。反之亦然,Start1本身的表达似乎依赖蜕皮激素,就像蜕皮激素缺乏的突变体ecd-1一样。 Start1表达严重降低。

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