RILP interacts with HOPS complex via VPS41 subunit to regulate endocytic trafficking.
RILP interacts with HOPS complex via VPS41 subunit to regulate endocytic trafficking.
复制标题
RILP 通过 VPS41 亚基与 HOPS 复合物相互作用，调节内吞运输。
DOI：
10.1038/srep07282
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发表时间：
2014-12-02
影响因子：
4.6
通讯作者：
Wang T
中科院分区：
文献类型：
--
作者：
Lin X;Yang T;Wang S;Wang Z;Yun Y;Sun L;Zhou Y;Xu X;Akazawa C;Hong W;Wang T
啤酒花复合体在酵母中作为一种与Ypt7p具有全球环境基金活性的系链复合体来调节晚期内膜成熟。虽然啤酒花复合体在酵母细胞中的作用已经得到了很好的证实，但它在哺乳动物细胞中的功能和机制还不是很清楚。在本研究中，我们报道了RILP，Rab7的下游效应器，与啤酒花复合体相互作用，并将啤酒花亚单位招募到晚期的内体隔室。在结构上，RILP的氨基末端部分与啤酒花复合体相互作用。出乎意料的是，这种互动是独立于Rab7的。HOPS复合体的VPS41亚基被定义为与RILP相互作用的主要伙伴。VPS41的羧基末端区域被定位为负责相互作用的区域。在功能上，通过shRNA耗尽VPS41或过度表达VPS41 C端可半抑制EGF诱导的EGFR降解。这些结果表明，RILP通过VPS41与啤酒花复合体相互作用在EGFR的胞内转运中发挥作用。
The HOPS complex serves as a tethering complex with GEF activity for Ypt7p in yeast to regulate late endosomal membrane maturation. While the role of HOPS complex is well established in yeast cells, its functional and mechanistic aspects in mammalian cells are less well defined. In this study, we report that RILP, a downstream effector of Rab7, interacts with HOPS complex and recruits HOPS subunits to the late endosomal compartment. Structurally, the amino-terminal portion of RILP interacts with HOPS complex. Unexpectedly, this interaction is independent of Rab7. VPS41 subunit of HOPS complex was defined to be the major partner for interacting with RILP. The carboxyl-terminal region of VPS41 was mapped to be responsible for the interaction. Functionally, either depletion of VPS41 by shRNA or overexpression of VPS41 C-terminal half retarded EGF-induced degradation of EGFR. These results suggest that interaction of RILP with HOPS complex via VPS41 plays a role in endocytic trafficking of EGFR.
影响因子：
4
作者：
van der Kant, Rik;Fish, Alexander;Neefjes, Jacques
通讯作者：
Neefjes, Jacques