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首页> 外文期刊>Molecular and Cellular Biology >Mutant Huntingtin Impairs Axonal Trafficking in Mammalian Neurons In Vivo and In Vitro
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Mutant Huntingtin Impairs Axonal Trafficking in Mammalian Neurons In Vivo and In Vitro

机译：突变的Huntingtin损害体内和体外哺乳动物神经元的轴突运输。

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Recent data in invertebrates demonstrated that huntingtin (htt) is essential for fast axonal trafficking. Here, we provide direct and functional evidence that htt is involved in fast axonal trafficking in mammals. Moreover, expression of full-length mutant htt (mhtt) impairs vesicular and mitochondrial trafficking in mammalian neurons in vitro and in whole animals in vivo. Particularly, mitochondria become progressively immobilized and stop more frequently in neurons from transgenic animals. These defects occurred early in development prior to the onset of measurable neurological or mitochondrial abnormalities. Consistent with a progressive loss of function, wild-type htt, trafficking motors, and mitochondrial components were selectively sequestered by mhtt in human Huntington's disease-affected brain. Data provide a model for how loss of htt function causes toxicity; mhtt-mediated aggregation sequesters htt and components of trafficking machinery leading to loss of mitochondrial motility and eventual mitochondrial dysfunction.
机译：无脊椎动物的最新数据表明，亨廷顿蛋白（htt）对于快速轴突运输至关重要。在这里，我们提供直接和功能性证据表明，htt参与哺乳动物的快速轴突运输。此外，全长突变体htt（mhtt）的表达会损害哺乳动物神经元在体外和整个动物体内的囊泡和线粒体运输。特别是，线粒体逐渐固定化并在转基因动物的神经元中更频繁地停止。这些缺陷发生在可测量的神经系统或线粒体异常发生之前的发育早期。与功能的逐步丧失相一致，野生型HTT，运输马达和线粒体成分被MHTt选择性地螯合在受亨廷顿病影响的人类大脑中。数据提供了htt功能丧失如何引起毒性的模型; mhtt介导的聚集螯合剂和运输工具的成分导致线粒体运动力丧失和最终的线粒体功能障碍。

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