HYPERVARIABLE C-TERMINAL DOMAIN OF RAB PROTEINS ACTS AS A TARGETING SIGNAL

HYPERVARIABLE C-TERMINAL DOMAIN OF RAB PROTEINS ACTS AS A TARGETING SIGNAL
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DOI:
10.1038/353769a0
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发表时间:
1991-10-24
期刊:
影响因子:
64.8
通讯作者:
ZERIAL, M
ZERIAL, M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
CHAVRIER, P;GORVEL, JP;ZERIAL, M

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哺乳动物细胞表达许多ras样低分子量GTP结合蛋白(rab蛋白)1-6,它们与参与控制酵母分泌的Ypt 1和Sec 4蛋白高度同源7-9。由于它们的结构相似性和它们的多样性,假设rab蛋白在胞吐和胞吞作用中充当膜运输的特异性调节剂10,并且rab 5已被证明参与体外早期内体融合11。与其假定的功能一致,迄今为止研究的所有rab蛋白质都发现在沿着胞吐或胞吞途径的不同亚室中沿着5,11 -13。为了确定介导其特异性定位的区域,我们在BHK细胞中瞬时表达rab 2,rab 5和rab 7杂合蛋白,并通过免疫荧光共聚焦显微镜和亚细胞分级分离确定其细胞内定位。在这里,我们提出的证据表明,高度可变的C-末端结构域包含必要的结构元件的关联rab蛋白与其特定的靶膜的内吞途径。
MAMMALIAN cells express many ras-like low molecular mass GTP-binding proteins (rab proteins) 1-6 that are highly homologous to the Ypt1 and Sec4 proteins involved in controlling secretion in yeast 7-9. Owing to their structural similarity and to their variety, rab proteins have been postulated to act as specific regulators of membrane traffic in exocytosis and endocytosis 10, and rab5 has been shown to be involved in early endosome fusion in vitro 11. In agreement with their postulated functions, all rab proteins studied so far have been found in distinct subcompartments along the exocytic or endocytic pathways 5,11-13. To define the region mediating their specific localization, we transiently expressed rab2, rab5 and rab7 hybrid proteins in BHK cells, and determined their intracellular localization by immunofluorescence confocal microscopy and subcellular fractionation. Here we present evidence that the highly variable C-terminal domain contains structural elements necessary for the association of rab proteins with their specific target membranes in the endocytic pathway.