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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Lightoid and Claret: A rab GTPase and its putative guanine nucleotide exchange factor in biogenesis of Drosophila eye pigment granules.
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Lightoid and Claret: A rab GTPase and its putative guanine nucleotide exchange factor in biogenesis of Drosophila eye pigment granules.

机译:Lightoid和Claret:果蝇眼色素颗粒生物发生中的一种rab GTPase及其推定的鸟嘌呤核苷酸交换因子。

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To elucidate the biogenetic pathways for the generation of lysosome-related organelles, we have chosen to study the Drosophila eye pigment granules because they are lysosome-related and the fruit fly provides the advantages of a genetic system in which many mutations affect eye color. Here, we report the molecular identification of two classic Drosophila eye-color genes required for pigment granule biogenesis, claret and lightoid; the former encodes a protein containing seven repeats with sequence similarity to those that characterize regulator of chromosome condensation 1 (RCC1, a guanine nucleotide exchange factor for the small GTPase, Ran), and the latter encodes a rab GTPase, Rab-RP1. We demonstrate in transfected cells that Claret, through its RCC1-like domain, interacts preferentially with the nucleotide-free form of Rab-RP1, and this interaction involves Claret's first three RCC1-like repeats that are also critical for Claret's function in pigment granule biogenesis in transgenic rescue experiments. In addition, double-mutant analyses suggest that the gene products of claret and lightoid function in the same pathway, which is different from that of garnet and ruby (which encode the delta- and beta-subunit of the tetrameric adaptor protein 3 complex, respectively). Taken together, our results suggest that Claret functions as a guanine nucleotide exchange factor for Lightoid/Rab-RP1 in an adaptor protein 3-independent vesicular trafficking pathway of pigment granule biogenesis.
机译:为了阐明产生溶酶体相关细胞器的生物遗传途径,我们选择研究果蝇眼色素颗粒,因为它们与溶酶体相关,并且果蝇提供了遗传系统的优势,在该系统中许多突变会影响眼睛的颜色。在这里,我们报告了色素颗粒生物发生所需的两个经典果蝇眼色基因的分子鉴定,即深紫红色和浅色。前者编码一种蛋白质,该蛋白质包含七个重复序列,这些重复序列与表征染色体浓缩1(RCC1,小GTPase的鸟嘌呤核苷酸交换因子,Ran)的调节子的序列相似,而后者编码一个rab GTPase,Rab-RP1。我们在转染的细胞中证明了Claret通过其RCC1样结构域优先与无核苷酸形式的Rab-RP1相互作用,并且这种相互作用涉及Claret的前三个RCC1样重复序列,这对于Claret在色素颗粒生物发生中的功能也至关重要在转基因救援实验中此外,双突变分析表明,紫红色和亮光蛋白的基因产物在相同的途径中起作用,这与石榴石和红宝石(分别编码四聚体衔接蛋白3复合体的δ和β亚基)不同。 )。两者合计,我们的结果表明,Claret在色素颗粒生物发生的衔接蛋白3非依赖性囊泡运输途径中充当Lightoid / Rab-RP1的鸟嘌呤核苷酸交换因子。

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