N4WBP5A (Ndfip2), a Nedd4-interacting protein, localizes to multivesicular bodies and the Golgi, and has a potential role in protein trafficking
N4WBP5A (Ndfip2), a Nedd4-interacting protein, localizes to multivesicular bodies and the Golgi, and has a potential role in protein trafficking
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DOI：
10.1242/jcs.01212
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发表时间：
2004-07-15
影响因子：
4
通讯作者：
Kumar, S
中科院分区：
文献类型：
--
作者：
Shearwin-Whyatt, LM;Brown, DL;Kumar, S
N4 WBP 5A（Ndfip 2）是一组进化上保守的Nedd 4相互作用蛋白，在哺乳动物中有两个同源物。我们以前已经表明，非洲爪蟾卵母细胞中N4 WBP 5A的表达增加上皮钠通道的细胞表面表达的结果。N4 WBP的特征在于一个或两个氨基末端PPxY基序和三个跨膜结构域。在这里，我们表明，两个PPxY基序的N4 WBP 5A介导的相互作用与WW域的Nedd 4和N4 WBP 5A可以物理相互作用的WW域的几个Nedd 4家族蛋白。N4 WBP 5A是泛素化的，并且泛素化不显著影响N4 WBP 5A蛋白的周转。N4 WBP 5A的泛素化通过Nedd 4和Nedd 4 -2表达增强。N4 WBP 5A定位于高尔基体、与高尔基体复合体相关的囊泡和多泡体。我们发现，异位表达的N4 WBP 5A抑制受体介导的标记表皮生长因子的内吞作用。N4 WBP 5A过表达抑制EGF在大的内吞/溶酶体囊泡中的积累，提示N4 WBP 5A在蛋白质运输中的作用。我们建议N4 WBP 5A作为一个适配器招募Nedd 4家族泛素蛋白连接酶的蛋白质运输机制。
N4WBP5A (Ndfip2) belongs to an evolutionarily conserved group of Nedd4-interacting proteins with two homologues in mammalian species. We have previously shown that N4WBP5A expression in Xenopus oocytes results in increased cell-surface expression of the epithelial sodium channel. N4WBPs are characterized by one or two amino terminal PPxY motifs and three transmembrane domains. Here we show that both PPxY motifs of N4WBP5A mediate interaction with WW domains of Nedd4 and that N4WBP5A can physically interact with the WW domains of several Nedd4-family proteins. N4WBP5A is ubiquitinated and ubiquitination does not significantly affect the turnover of N4WBP5A protein. Ubiquitination of N4WBP5A is enhanced by Nedd4 and Nedd4-2 expression. N4WBP5A localizes to the Golgi, vesicles associated with the Golgi complex and to multivesicular bodies. We show that the ectopic expression of N4WBP5A inhibits receptor-mediated endocytosis of labelled epidermal growth factor. N4WBP5A overexpression inhibits accumulation of EGF in large endocytic/lysosomal vesicles suggestive of a role for N4WBP5A in protein trafficking. We propose that N4WBP5A acts as an adaptor to recruit Nedd4 family ubiquitin-protein ligases to the protein trafficking machinery.