PtdIns4KIIα generates endosomal PtdIns(4)P and is required for receptor sorting at early endosomes.
PtdIns4KIIα generates endosomal PtdIns(4)P and is required for receptor sorting at early endosomes.
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PTDINS4KIIα会产生内体PTDINS（4）P，是早期内体的受体分类所必需的。
DOI：
10.1091/mbc.e15-08-0564
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发表时间：
2016-03-15
影响因子：
3.3
通讯作者：
Tanabe K
中科院分区：
文献类型：
--
作者：
Henmi Y;Morikawa Y;Oe N;Ikeda N;Fujita A;Takei K;Minogue S;Tanabe K
PtdIns 4KII α参与了内体运输的调节，但其酶活性的作用及其作用位点尚未阐明。PtdIns 4KII α的缺失显著减少了早期内体上囊泡状PtdIns（4）P的量，使细胞从早期内体分选分子的能力受损。磷脂酰肌醇4-激酶IIα（PtdIns 4KII α）定位于高尔基体网络和内体区室，并参与内体运输的调节，但其酶活性及其作用位点的作用尚未阐明。这项研究表明，PtdIns 4KII α是在早期内体上产生内体磷脂酰肌醇4-磷酸（PtdIns（4）P）以及将转铁蛋白和表皮生长因子受体分选到再循环和降解途径所必需的。用小干扰RNA去除PtdIns 4KII α显著减少了早期内体上囊泡状PtdIns（4）P的数量，但高尔基体膜上没有。缺失PtdIns 4KII α的细胞对从早期内体中回收的分子进行分选的能力受损。我们进一步鉴定了Eps 15同源结构域蛋白3（EHD 3）作为PtdIns 4KII α的可能的内体效应子。在PtdIns 4KII α缺失的细胞中，含有EHD 3的管状内体缩短，变得更加囊泡化。在PtdIns 4KII α缺失的细胞中，内体PtdIns（4，5）P2也显著减少。这些结果表明，PtdIns 4KII α通过PtdIns（4）P依赖性途径调节早期内体的受体分选，并为内体PtdIns（4，5）P2的合成提供底物。
PtdIns4KIIα has been implicated in the regulation of endosomal traffic, but the role of its enzymatic activity and the site of its action have not been elucidated. Depletion of PtdIns4KIIα significantly reduced the amount of vesicular PtdIns(4)P on early endosomes, leaving cells with an impaired ability to sort molecules from early endosomes. Phosphatidylinositol 4-kinase IIα (PtdIns4KIIα) localizes to the trans-Golgi network and endosomal compartments and has been implicated in the regulation of endosomal traffic, but the roles of both its enzymatic activity and the site of its action have not been elucidated. This study shows that PtdIns4KIIα is required for production of endosomal phosphatidylinositol 4-phosphate (PtdIns(4)P) on early endosomes and for the sorting of transferrin and epidermal growth factor receptor into recycling and degradative pathways. Depletion of PtdIns4KIIα with small interfering RNA significantly reduced the amount of vesicular PtdIns(4)P on early endosomes but not on Golgi membranes. Cells depleted of PtdIns4KIIα had an impaired ability to sort molecules destined for recycling from early endosomes. We further identify the Eps15 homology domain–containing protein 3 (EHD3) as a possible endosomal effector of PtdIns4KIIα. Tubular endosomes containing EHD3 were shortened and became more vesicular in PtdIns4KIIα-depleted cells. Endosomal PtdIns(4,5)P2 was also significantly reduced in PtdIns4KIIα-depleted cells. These results show that PtdIns4KIIα regulates receptor sorting at early endosomes through a PtdIns(4)P-dependent pathway and contributes substrate for the synthesis of endosomal PtdIns(4,5)P2.