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

Cell Stem Cell. 2020 Feb 27.

Christopher S Morrow¹, Tiaira J Porter¹, Nan Xu¹, Zachary P Arndt¹, Kayla Ako-Asare¹, Helen J Heo¹, Elizabeth A N Thompson¹, Darcie L Moore²

1. Department of Neuroscience, University of Wisconsin - Madison, Madison, WI 53705, USA.
2. Department of Neuroscience, University of Wisconsin - Madison, Madison, WI 53705, USA. Electronic address: darcie.moore@wisc.edu.

Abstract

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.

Presented by Christopher Morrow