Proteostatic control of quiescence exit in mammalian neural stem cells
Somatic stem cells must maintain a healthy proteome throughout life to support tissue homeostasis, however, the complexities of the stem cell response to increased damaged or aggregated proteins remain unclear.
Monday 11 November 2019 (12h15 - 13h00) - Bugnon 7 - Seminar room, 6th floor
Previously it was shown in cell lines that following impaired proteostasis, damaged proteins are trafficked to the centrosome and surrounded by the intermediate filament vimentin in a structure called an aggresome. The endogenous role of aggresomes and how they specifically enhance recovery from disrupted proteostasis has remained elusive. We found that adult neural stem cells (NSCs) utilize aggresomes to recover from imbalanced proteostasis, and describe a novel function for vimentin in proteostasis as a spatial coordinator of proteasomes to the aggresome. In the absence of vimentin, aggresomes can still form, however proteasomes are not localized to the aggresome, leading to an inability of NSCs to recover from cellular stress. During quiescence exit, a time when NSCs are required to clear a wave of aggregated proteins, we find in vitro and in vivo that vimentin KO NSCs have a reduced capacity to exit quiescence, and have disrupted neurogenesis during aging. Taken together, these data demonstrate a significant role for vimentin and aggresomes in the regulation of proteostasis during quiescent NSC activation.
Département de Physiologie