The DnaJ-domain protein RME-8 functions in endosomal trafficking
The DnaJ-domain protein RME-8 functions in endosomal trafficking
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DOI：
10.1074/jbc.m505036200
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发表时间：
2005-12-02
影响因子：
4.8
通讯作者：
McPherson, PS
中科院分区：
文献类型：
--
作者：
Girard, M;Poupon, V;McPherson, PS
通过对大鼠肝脏网格蛋白包被囊泡的蛋白质组学分析，我们确定了受体介导的内吞作用8（RME-8）的哺乳动物同源物，RME-8是一种含有DnaJ结构域的蛋白质，最初在秀丽隐杆线虫的内吞缺陷筛选中被确定。哺乳动物RME-8具有广泛的组织分布，亲和选择测定揭示了无处不在的伴侣Hsc 70，其调节蛋白质构象在不同的膜位点作为其DnaJ结构域的主要结合伴侣。RME-8与微粒体膜紧密结合，并与内体系统的标志物共定位。小干扰RNA介导的RME-8敲低对转铁蛋白内吞作用没有影响，但导致表皮生长因子内化减少。有趣的是，与定位于内体一致，RME-8的敲低也导致阳离子非依赖性甘露糖6-磷酸受体的运输改变和溶酶体水解酶组织蛋白酶D的不正确分选。我们的数据表明，RME-8的功能，在细胞内的运输，并提供了第一个证据的功能作用的DnaJ结构域轴承共伴侣的内涵体。
Through a proteomic analysis of clathrin-coated vesicles from rat liver we identified the mammalian homolog of receptor-mediated endocytosis 8 ( RME-8), a DnaJ domain-containing protein originally identified in a screen for endocytic defects in Caenorhabditis elegans. Mammalian RME-8 has a broad tissue distribution, and affinity selection assays reveal the ubiquitous chaperone Hsc70, which regulates protein conformation at diverse membrane sites as the major binding partner for its DnaJ domain. RME-8 is tightly associated with microsomal membranes and co-localizes with markers of the endosomal system. Small interfering RNA-mediated knock down of RME-8 has no influence on transferrin endocytosis but causes a reduction in epidermal growth factor internalization. Interestingly, and consistent with a localization to endosomes, knock down of RME-8 also leads to alterations in the trafficking of the cation-independent mannose 6-phosphate receptor and improper sorting of the lysosomal hydrolase cathepsin D. Our data demonstrate that RME-8 functions in intracellular trafficking and provides the first evidence of a functional role for a DnaJ domain-bearing co-chaperone on endosomes.