Late endosome motility depends on lipids via the small GTPase Rab7
Late endosome motility depends on lipids via the small GTPase Rab7
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DOI：
10.1093/emboj/21.6.1289
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发表时间：
2002-03-15
期刊：
影响因子：
11.4
通讯作者：
Gruenberg, J
中科院分区：
文献类型：
--
作者：
Lebrand, C;Corti, M;Gruenberg, J
我们报告，脂质有助于调节后期内吞隔室的双向运动。晚期内吞囊泡装载胆固醇失去其动力学特性，变得基本上不动，包括在尼曼-匹克C患者的细胞中。这些囊泡然后保留细胞质动力蛋白活性，但似乎无法获得驱动蛋白活性，最终导致瘫痪。我们的数据表明，这种缺陷依赖于小GTdR Rab 7，因为Rab 7抑制突变体N125 I可以恢复载胆固醇的囊泡的运动性。相反，野生型Rab 7过表达模拟胆固醇对对照细胞运动性的影响。一致地，胆固醇积累增加膜相关Rab 7的量，并且通过鸟嘌呤核苷酸解离抑制剂抑制Rab 7膜提取。因此，我们的观察结果表明，胆固醇有助于调节Rab 7周期，Rab 7反过来控制晚期内吞元件的净运动。我们的结论是，运动功能可以通过Rab 7循环的膜脂质组合物进行调节。
We report that lipids contribute to regulate the bidirectional motility of late endocytic compartments. Late endocytic vesicles loaded with cholesterol lose their dynamic properties, and become essentially immobile, including in cells from Niemann-Pick C patients. These vesicles then retain cytoplasmic dynein activity, but seem to be unable to acquire kinesin activity, eventually leading to paralysis. Our data suggest that this defect depends on the small GTPase Rab7, since the motility of vesicles loaded with cholesterol can be restored by the Rab7 inhibitory mutant N125I. Conversely, wild-type Rab7 overexpression mimics the effects of cholesterol on motility in control cells. Consistently, cholesterol accumulation increases the amounts of membrane-associated Rab7, and inhibits Rab7 membrane extraction by the guanine nucleotide dissociation inhibitor. Our observations thus indicate that cholesterol contributes to regulate the Rab7 cycle, and that Rab7 in turn controls the net movement of late endocytic elements. We conclude that motor functions can be regulated by the membrane lipid composition via the Rab7 cycle.