Rabaptin4, a novel effector of the small GTPase rab4a, is recruited to perinuclear recycling vesicles
Rabaptin4, a novel effector of the small GTPase rab4a, is recruited to perinuclear recycling vesicles
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DOI：
10.1042/0264-6021:3460593
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发表时间：
2000-03-15
影响因子：
4.1
通讯作者：
van der Sluijs, P
中科院分区：
文献类型：
--
作者：
Nagelkerken, B;van Anken, E;van der Sluijs, P
小的GTP酶Rab4a与早期的内吞细胞室相关，并调节早期内小体的受体循环。为了了解Rab4a是如何调节其功能的，我们寻找了与该GTP酶相关的蛋白质，并调节其在细胞内转运的活性。在此，我们鉴定了Rabaptin4，这是一种新的Rab4a效应分子。Rabaptin4与Rabaptin5同源，并含有Rabaptin5的C端缺失，Rabaptin4优先与Rab4a-GTP相互作用，少量与Rab5aGTP相互作用。我们在Rabaptin4的N端区域发现了一个Rab4a结合域，并确定了Rab5的两个结合位点，其中包括一个新的N端Rab5a结合位点。Rabaptin4是一种胞质蛋白，能抑制Rab4a固有的GTP水解率，并被Rab4a-GTP募集来回收富含细胞红素和内化的吲哚菁蓝-3(Cy3)标记的转铁蛋白的内体。我们认为Rabaptin4在从早期内小体到再循环内小体的运输小泡对接过程中起辅助作用。
The small GTPase rab4a is associated with early endocytic compartments and regulates receptor recycling from early endosomes. To understand how rab4a mediates its function, we searched for proteins which associate with this GTPase and regulate its activity in endocytic transport. Here we identified rabaptin4, a novel effector molecule of rab4a. Rabaptin4 is homologous with rabaptin5 and contains a C-terminal deletion with respect to rabaptin5, Rabaptin4 preferentially interacts with rab4a-GTP and to a lesser extent with rab5aGTP. We identified a rab4a-binding domain in the N-terminal region of rabaptin4, and two binding sites for rab5, including a novel N-terminal rab5a-binding site. Rabaptin4 is a cytosolic protein that inhibits the intrinsic GTP hydrolysis rate of rab4a and is recruited by rab4a-GTP to recycling endosomes enriched in cellubrevin and internalized indocarbocyanine-3 (Cy3)-labelled transferrin. We propose that rabaptin4 assists in the docking of transport vesicles en route from early endosomes to recycling endosomes.