Caenorhabditis elegans RME-6 is a novel regulator of RAB-5 at the clathrin-coated pit
Caenorhabditis elegans RME-6 is a novel regulator of RAB-5 at the clathrin-coated pit
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DOI：
10.1038/ncb1261
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发表时间：
2005-06-01
影响因子：
21.3
通讯作者：
Grant, BD
中科院分区：
文献类型：
--
作者：
Sato, M;Sato, K;Grant, BD
在这里，我们确定了一个新的内吞作用的调节称为RME-6。RME-6在后生动物中进化保守，包含Ras-GAP（GTP酶激活蛋白）样结构域和Vps 9结构域。与已知的Vps 9结构域在Rab 5 GDP/GTP交换中的催化功能一致，我们发现RME-6以GDP结合构象特异性结合秀丽隐杆线虫RAB-5，并且rme-6突变体具有指示低RAB-5活性的表型。然而，与其他Rab 5相关蛋白不同，拯救绿色荧光蛋白（GFP）-RME-6融合蛋白主要定位于网格蛋白包被的凹坑，与α-适配蛋白（网格蛋白适配蛋白）物理相互作用，并需要网格蛋白来实现其皮质定位。在rme-6突变体中，从质膜到内体的转运是有缺陷的，并且小的110-nm内吞囊泡就在质膜下方积累。这些结果表明，Rab 5在网格蛋白包被的凹坑或网格蛋白包被的囊泡中的激活机制对于将内吞货物递送到早期内体是必需的。
Here we identify a new regulator of endocytosis called RME-6. RME-6 is evolutionarily conserved among metazoans and contains Ras-GAP (GTPase-activating protein)-like and Vps9 domains. Consistent with the known catalytic function of Vps9 domains in Rab5 GDP/GTP exchange, we found that RME-6 binds specifically to Caenorhabditis elegans RAB-5 in the GDP-bound conformation, and rme-6 mutants have phenotypes that indicate low RAB-5 activity. However, unlike other Rab5-associated proteins, a rescuing green fluorescent protein (GFP)-RME-6 fusion protein primarily localizes to clathrin-coated pits, physically interacts with alpha-adaptin, a clathrin adaptor protein, and requires clathrin to achieve its cortical localization. In rme-6 mutants, transport from the plasma membrane to endosomes is defective, and small 110-nm endocytic vesicles accumulate just below the plasma membrane. These results suggest a mechanism for the activation of Rab5 in clathrin-coated pits or clathrin-coated vesicles that is essential for the delivery of endocytic cargo to early endosomes.