A role for Hrs in endosomal sorting of ligand-stimulated and unstimulated epidermal growth factor receptor
A role for Hrs in endosomal sorting of ligand-stimulated and unstimulated epidermal growth factor receptor
复制标题
DOI：
10.1016/j.yexcr.2004.03.038
复制
发表时间：
2004-07-15
影响因子：
3.7
通讯作者：
Kitamura, N
中科院分区：
文献类型：
--
作者：
Morino, C;Kato, M;Kitamura, N
配体刺激的生长因子受体迅速内化并转运至早期内体。未受刺激的受体也被组成性内化，尽管速率较慢，并被递送到相同的细胞器。在早期的内体，受刺激的受体被分选用于溶酶体降解途径，而未受刺激的受体大多被再循环回到细胞表面。为了研究早期内体蛋白Hrs在分选过程中的作用，我们在HeLa细胞中过表达Hrs，并研究了表皮生长因子受体（EGFR）在EGF刺激和未刺激细胞中的细胞内运输。Hrs的过表达抑制EGFR从早期内体的运输，导致EGFR在配体刺激和未刺激的细胞中在早期内体上的积累。另一方面，在FYVE结构域内具有缺失或点突变的Hrs突变体的过表达不抑制贩运。这些结果表明，Hrs调节配体刺激和未刺激的生长因子受体的分选早期内体，和FYVE域，这是所需的Hrs驻留在早期内体的微域，起着至关重要的作用，在功能的Hrs。(C)2004年爱思唯尔公司All rights reserved.
Ligand-stimulated growth factor receptors are rapidly internalized and transported to early endosomes. Unstimulated receptors are also internalized constitutively, although at a slower rate, and delivered to the same organelle. At early endosomes, stimulated receptors are sorted for the lysosomal degradation pathway, whereas unstimulated receptors are mostly recycled back to the cell surface. To investigate the role of Hrs, an early endosomal protein, in this sorting process, we overexpressed Hrs in HeLa cells and examined the intracellular trafficking of epidermal growth factor receptor (EGFR) in EGF-stimulated and unstimulated cells. Overexpression of Hrs inhibited the trafficking of EGFR from early endosomes, resulting in an accumulation of EGFR on early endosomes in both ligand-stimulated and unstimulated cells. On the other hand, overexpression of Hrs mutants with a deletion or a point mutation within the FYVE domain did not inhibit the trafficking. These results suggest that Hrs regulates the sorting of ligand-stimulated and unstimulated growth factor receptors on early endosomes, and that the FYVE domain, which is required for Hrs to reside in a microdomain of early endosomes, plays an essential role in the function of Hrs. (C) 2004 Elsevier Inc. All rights reserved.