Hrs recruits clathrin to early endosomes
Hrs recruits clathrin to early endosomes
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DOI：
10.1093/emboj/20.17.5008
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发表时间：
2001-09-03
期刊：
影响因子：
11.4
通讯作者：
Stenmark, H
中科院分区：
文献类型：
--
作者：
Raiborg, C;Bache, KG;Stenmark, H
肝细胞生长因子调节的酪氨酸激酶底物Hrs参与细胞内运输和信号转导。Hrs含有磷脂酰肌醇3-磷酸结合FYVE结构域，有助于其内体靶向。在这里，我们表明，Hrs和EEA 1，一个FYVE结构域蛋白参与内吞膜融合，定位于早期内涵体的不同区域。我们证明了Hrs与网格蛋白共定位，并且Hrs的C-末端含有直接与网格蛋白重链的末端β-螺旋桨结构域相互作用的功能性网格蛋白盒基序。在用Hrs转染的细胞中观察到网格蛋白向早期内体的大量募集，但用缺乏C-末端的Hrs转染的细胞则没有。此外，磷脂酰肌醇3-激酶抑制剂渥曼青霉素引起Hrs和网格蛋白从内体解离。虽然Hrs的过度表达不影响转铁蛋白的内吞和再循环，但内吞的表皮生长因子和葡聚糖保留在早期内体中。这些结果提供了一个分子机制，招募网格蛋白到早期内涵体，并建议在运输从早期到晚期内涵体的功能。
The hepatocyte growth factor-regulated tyrosine kinase substrate, Hrs, has been implicated in intracellular trafficking and signal transduction. Hrs contains a phosphatidylinositol 3-phosphate-binding FYVE domain that contributes to its endosomal targeting. Here we show that Hrs and EEA1, a FYVE domain protein involved in endocytic membrane fusion, are localized to different regions of early endosomes. We demonstrate that Hrs co-localizes with clathrin, and that the C-terminus of Hrs contains a functional clathrin box motif that interacts directly with the terminal beta -propeller domain of clathrin heavy chain. A massive recruitment of clathrin to early endosomes was observed in cells transfected with Hrs, but not with Hrs lacking the C-terminus. Furthermore, the phosphatidylinositol 3-kinase inhibitor wortmannin caused the dissociation of both Hrs and clathrin from endosomes. While overexpression of Hrs did not affect endocytosis and recycling of transferrin, endocytosed epidermal growth factor and dextran were retained in early endosomes. These results provide a molecular mechanism for the recruitment of clathrin onto early endosomes and suggest a function for Hrs in trafficking from early to late endosomes.