Morrow Christopher S, Porter Tiaira J, Xu Nan, Arndt Zachary P, Ako-Asare Kayla, Heo Helen J, Thompson Elizabeth A N, Moore Darcie L
Department of Neuroscience, University of Wisconsin - Madison, Madison, WI 53705, USA.
Department of Neuroscience, University of Wisconsin - Madison, Madison, WI 53705, USA.
Cell Stem Cell. 2020 Apr 2;26(4):558-568.e9. doi: 10.1016/j.stem.2020.01.018. Epub 2020 Feb 27.
Maintaining a healthy proteome throughout life is critical for proper somatic stem cell function, but the complexities of the stem cell response to increases in damaged or aggregated proteins remain unclear. Here we demonstrate that adult neural stem cells (NSCs) utilize aggresomes to recover from disrupted proteostasis and describe a novel function for the intermediate filament vimentin in proteostasis as a spatial coordinator of proteasomes to the aggresome. In the absence of vimentin, NSCs have a reduced capacity to exit quiescence, a time when NSCs are required to clear a wave of aggregated proteins, and demonstrate an early age-dependent decline in proliferation and neurogenesis. Taken together, these data reveal a significant role of vimentin and aggresomes in the regulation of proteostasis during quiescent NSC activation.
终生维持健康的蛋白质组对于体细胞干细胞的正常功能至关重要，但干细胞对受损或聚集蛋白增加的反应的复杂性仍不清楚。在这里，我们证明成年神经干细胞（NSCs）利用聚集体从破坏的蛋白质稳态中恢复，并描述了中间丝波形蛋白在蛋白质稳态中的一种新功能，即作为蛋白酶体到聚集体的空间协调者。在没有波形蛋白的情况下，神经干细胞退出静止期的能力降低，静止期是神经干细胞需要清除一波聚集蛋白的时期，并且表现出增殖和神经发生的早期年龄依赖性下降。综上所述，这些数据揭示了波形蛋白和聚集体在静止神经干细胞激活过程中对蛋白质稳态调节的重要作用。
