Vimentin Coordinates Protein Turnover at the Aggresome during Neural Stem Cell Quiescence Exit

• Published in: Cell stem cell 2020-04, Vol.26 (4), p.558-568.e9
• Main Authors: Morrow, Christopher S., Porter, Tiaira J., Xu, Nan, Arndt, Zachary P., Ako-Asare, Kayla, Heo, Helen J., Thompson, Elizabeth A.N., Moore, Darcie L.
• Format: Article
• Language: English
• Subjects: Adult Stem Cells; aggresome; Humans; Intermediate Filaments; neural stem cell; Neural Stem Cells; Neurogenesis; proteasome; proteostasis; quiescence; Vimentin
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2020.01.018

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. [Display omitted] •Mammalian NSCs utilize vimentin-caged aggresomes to recover proteostasis•Vimentin is required for proteasome localization to the aggresome in NSCs•Quiescent NSCs upregulate vimentin protein and utilize aggresomes during activation•Vimentin knockout in NSCs impairs proteostasis recovery and delays quiescence exit Recent evidence suggests that neural stem cell (NSC) quiescence exit is a significant barrier to adult neurogenesis. Morrow et al. reveal that NSCs rely on vimentin-mediated proteasome localization to the aggresome to clear proteins during quiescence exit and uncover a critical role of vimentin as a regulator of cellular proteostasis.