A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function
A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function
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DOI：
10.1016/s0092-8674(00)80380-3
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发表时间：
1997-09-19
期刊：
影响因子：
64.5
通讯作者：
Zerial, M
中科院分区：
文献类型：
--
作者：
Horiuchi, H;Lippe, R;Zerial, M
小GTTRab 5在内吞运输中起重要作用。Rab GDP解离抑制剂将Rab 5递送至膜，其中核苷酸交换活性允许募集效应蛋白Rabaptin-5。在这里，我们发现了一种新的60 kDa Rab 5结合蛋白，Rabex-5。Rabex-5与Rabaptin-5形成紧密的物理复合物，并且该复合物对于内吞膜融合是必需的。哺乳动物Rabex-5的纳米电喷雾质谱和克隆测序显示惊人的同源性Vps 9 p，酵母蛋白参与内吞交通。Rabex-5在将GTP酶递送至膜后在Rab 5上显示GDP/GTP交换活性。这表明，一个可溶性交换因子耦合到一个Rab效应易位从胞质溶胶的膜，在那里的复合物稳定的活性状态的GTdR。
The small GTPase Rab5 plays an essential role in endocytic traffic. Rab GDP dissociation inhibitor delivers Rab5 to the membrane, where a nucleotide exchange activity allows recruitment of an effector protein, Rabaptin-5. Here we uncovered a novel 60 kDa Rab5-binding protein, Rabex-5. Rabex-5 forms a tight physical complex with Rabaptin-5, and this complex is essential for endocytic membrane fusion. Sequencing of mammalian Rabex-5 by nanoelectrospray mass spectrometry and cloning revealed striking homology to Vps9p, a yeast protein implicated in endocytic traffic. Rabex-5 displays GDP/GTP exchange activity on Rab5 upon delivery of the GTPase to the membrane. This demonstrates that a soluble exchange factor coupled to a Rab effector translocates from cytosol to the membrane, where the complex stabilizes the GTPase in the active state.