Functional genomics reveals genes involved in protein secretion and Golgi organization

Functional genomics reveals genes involved in protein secretion and Golgi organization
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DOI:
10.1038/nature04377
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发表时间:
2006-02-02
期刊:
影响因子:
64.8
通讯作者:
Malhotra, V
Malhotra, V
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bard, F;Casano, L;Malhotra, V

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酵母遗传学和体外生化分析已经确定了许多与蛋白质分泌有关的基因(1,2)。然而,与酵母菌相比,后生动物的分泌途径更为复杂,许多调节高尔基体组织的机制仍未得到充分研究。我们在果蝇细胞系中进行了全基因组RNA介导的干扰筛选,以确定组成蛋白分泌所需的基因。然后,我们根据这些基因的枯竭对高尔基体膜组织的影响进行了分类。结果表明,A类基因缺失使高尔基体膜重新分布到内质网中,B类基因缺失导致高尔基体碎裂,C类基因缺失导致高尔基体膜聚集,D类基因缺失对高尔基膜无明显影响。到目前为止,在20个新的基因产物中,有几个定位于高尔基体膜和内质网。
Yeast genetics and in vitro biochemical analysis have identified numerous genes involved in protein secretion(1,2). As compared with yeast, however, the metazoan secretory pathway is more complex and many mechanisms that regulate organization of the Golgi apparatus remain poorly characterized. We performed a genome-wide RNA-mediated interference screen in a Drosophila cell line to identify genes required for constitutive protein secretion. We then classified the genes on the basis of the effect of their depletion on organization of the Golgi membranes. Here we show that depletion of class A genes redistributes Golgi membranes into the endoplasmic reticulum, depletion of class B genes leads to Golgi fragmentation, depletion of class C genes leads to aggregation of Golgi membranes, and depletion of class D genes causes no obvious change. Of the 20 new gene products characterized so far, several localize to the Golgi membranes and the endoplasmic reticulum.