Visualization of cell-to-cell transmission of mutant huntingtin oligomers.
Visualization of cell-to-cell transmission of mutant huntingtin oligomers.
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DOI：
10.1371/currents.rrn1210
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发表时间：
2011-02-11
期刊：
影响因子：
--
通讯作者：
Outeiro TF
中科院分区：
文献类型：
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作者：
Herrera F;Tenreiro S;Miller-Fleming L;Outeiro TF
我们开发了一种新的细胞模型，用于活细胞中毒性亨廷顿寡聚体的可视化。将亨廷顿蛋白外显子1（25Q或103Q）融合到Venus蛋白的非荧光半部分。当亨廷顿蛋白在细胞内二聚化时，Venus在功能上重新构建并发出荧光。通过几种程序评估突变亨廷顿蛋白的寡聚化、聚集和毒性。我们还提出的证据表明，细胞之间的亨廷顿蛋白的传输可以用我们的模型以定量的方式确定。因此，该模型可以是一个强大的筛选工具，用于鉴定寡聚化修饰剂和突变亨廷顿蛋白的细胞间运输。
We developed a new cell model for the visualization of toxic huntingtin oligomers in living cells. Huntingtin exon 1 (25Q or 103Q) was fused to non-fluorescent halves of the Venus protein. When huntingtin dimerizes inside the cells, Venus becomes functionally reconstituted and emits fluorescence. Oligomerization, aggregation and toxicity of mutant huntingtin were assessed by several procedures. We also present evidence that the transmission of huntingtin between cells can be determined in a quantitative manner with our model. Thus, this model can be a powerful screening tool for the identification of modifiers of oligomerization and cell-to-cell traffic of mutant huntingtin.