KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), Leuven, Belgium.
VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium.
Sci Rep. 2019 Oct 31;9(1):15728. doi: 10.1038/s41598-019-52035-6.
Repeat expansions in the C9orf72 gene cause amyotrophic lateral sclerosis and frontotemporal dementia characterized by dipeptide-repeat protein (DPR) inclusions. The toxicity associated with two of these DPRs, poly-GR and poly-PR, has been associated with nucleocytoplasmic transport. To investigate the causal role of poly-GR or poly-PR on active nucleocytoplasmic transport, we measured nuclear import and export in poly-GR or poly-PR expressing Hela cells, neuronal-like SH-SY5Y cells and iPSC-derived motor neurons. Our data strongly indicate that poly-GR and poly-PR do not directly impede active nucleocytoplasmic transport.
C9orf72 基因中的重复扩展会导致肌萎缩侧索硬化症和额颞叶痴呆，其特征是二肽重复蛋白 (DPR) 包含物。两种 DPR 中的聚-GR 和聚-PR 与核细胞质转运有关，与毒性有关。为了研究聚-GR 或聚-PR 对活跃的核细胞质转运的因果作用，我们测量了表达聚-GR 或聚-PR 的 Hela 细胞、类神经元 SH-SY5Y 细胞和 iPSC 衍生的运动神经元中的核输入和输出。我们的数据强烈表明，聚-GR 和聚-PR 不会直接阻碍活跃的核细胞质转运。
