A GTPase-activating protein controls Rab5 function in endocytic trafficking
A GTPase-activating protein controls Rab5 function in endocytic trafficking
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DOI：
10.1038/ncb1290
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发表时间：
2005-09-01
影响因子：
21.3
通讯作者：
Barr, FA
中科院分区：
文献类型：
--
作者：
Haas, AK;Fuchs, E;Barr, FA
Rab家族GTP酶是膜运输的保守调节剂，在非活性GDP结合和活化GTP结合状态之间循环（1，2）. Rab函数的关键决定因素是GTP结合态的寿命（3）。由于Rabs具有低的固有GTP水解速率，因此该过程受GTP水解激活蛋白（GAP）的控制（1）。由于人类基因组编码的大量Rab和GAP，已经证明很难将特定的功能关系分配给这些蛋白质。在这里，我们确定了Rab 5特异性GAP（RabGAP 5），并显示RN-Tre（以前描述为Rab 5 GAP）作用于Rab 41。RabGAP- 5过表达触发Rab 5效应子EEA 1从内体的丢失并阻断内吞运输。相比之下，RabGAP- 5的消耗导致内体大小增加，更多的内体相关EEA 1，并破坏EGF和LAMP 1的运输。RabGAP- 5因此限制了激活的Rab 5的量，从而调节通过内体的运输。
Rab- family GTPases are conserved regulators of membrane trafficking that cycle between inactive GDP- bound and activated GTP- bound states(1,2). A key determinant of Rab function is the lifetime of the GTP- bound state(3). As Rabs have a low intrinsic rate of GTP hydrolysis, this process is under the control of GTP-hydrolysis-activating proteins ( GAPs) (1). Due to the large number of Rabs and GAPs that are encoded by the human genome, it has proven difficult to assign specific functional relationships to these proteins. Here, we identify a Rab5- specific GAP ( RabGAP5), and show that RN- Tre ( previously described as a Rab5 GAP) acts on Rab41. RabGAP- 5 overexpression triggers a loss of the Rab5 effector EEA1 from endosomes and blocks endocytic trafficking. By contrast, depletion of RabGAP- 5 results in increased endosome size, more endosome- associated EEA1, and disrupts the trafficking of EGF and LAMP1. RabGAP- 5 therefore limits the amount of activated Rab5, and thereby regulates trafficking through endosomes.