TIP47 is a key effector for Rab9 localization.
TIP47 is a key effector for Rab9 localization.
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DOI：
10.1083/jcb.200510010
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发表时间：
2006-06-19
期刊：
影响因子：
--
通讯作者：
Pfeffer S
中科院分区：
文献类型：
--
作者：
Aivazian D;Serrano RL;Pfeffer S
人类基因组编码定位于不同膜区室表面的1070 Rab GTP酶。为了研究Rab定位的机制，产生含有异源Rab高变结构域的嵌合体，并定量它们结合七种Rab效应物的能力。两个嵌合体可以结合两个明显本地化的Rabs效应器; Rab 5/9杂交结合Rab 5和Rab 9效应器，Rab 1/9杂交结合某些Rab 1和Rab 9效应器。这些不寻常的嵌合体允许测试的重要性效应器结合Rab本地化。在这两种情况下，改变细胞浓度的一个关键Rab 9效应，这是所谓的尾巴相互作用蛋白的47 kD，移动一小部分的蛋白质从他们的父母Rab本地化的Rab 9。因此，某些竞争效应物的相对浓度可以决定嵌合体的定位。这些数据证实了效应子相互作用对Rab 9定位的重要性，并支持效应子蛋白依赖于Rabs的模型，正如Rabs依赖于效应子来实现其正确的稳态定位一样。
The human genome encodes ∼70 Rab GTPases that localize to the surfaces of distinct membrane compartments. To investigate the mechanism of Rab localization, chimeras containing heterologous Rab hypervariable domains were generated, and their ability to bind seven Rab effectors was quantified. Two chimeras could bind effectors for two distinctly localized Rabs; a Rab5/9 hybrid bound both Rab5 and Rab9 effectors, and a Rab1/9 hybrid bound to certain Rab1 and Rab9 effectors. These unusual chimeras permitted a test of the importance of effector binding for Rab localization. In both cases, changing the cellular concentration of a key Rab9 effector, which is called tail-interacting protein of 47 kD, moved a fraction of the proteins from their parental Rab localization to that of Rab9. Thus, relative concentrations of certain competing effectors could determine a chimera's localization. These data confirm the importance of effector interactions for Rab9 localization, and support a model in which effector proteins rely on Rabs as much as Rabs rely on effectors to achieve their correct steady state localizations.
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