Effects and regulation of proteostasis in the activation of adult stem cells
Noelia was trained as a developmental neurobiologist in Barcelona. During her postdoc in London her focus shifted towards adult hippocampal neurogenesis. Currently at IMBA in Vienna, her group investigates how adult neural stem cells respond to systemic stimuli.
- Institute IMBA - Institute of Molecular Biotechnology
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Controlled protein degradation is critical during cellular transitions, like differentiation or exit from quiescence. When cells change their state, they must ensure not only that new gene products are generated but also that old cellular determinants that were locking their previous state are efficiently eliminated. We investigate the role and regulation of proteostasis in the transition of adult hippocampal stem cells from quiescence to activation.
In the hippocampus, adult neural stem cells (aNSCs) generate new neurons that modulate memory, stress and anxiety. Most aNSCs are in a resting state called quiescence, and their recruitment into the cell cycle is the most important regulatory step in adult neurogenesis. Systemic stimuli, such as exercise, diet or stress have a great impact on adult neurogenesis, but little is known about how aNSC quiescence is regulated by these stimuli.
We previously found that the E3-ubiquitin ligase Huwe1 is essential to allow the return to quiescence of activated aNSCs but has little effect on quiescent aNSCs. This has led us to hypothesize that quiescent and active stem cells might use different strategies for protein degradation. Indeed, proteostasis is a major regulator of aNSCs, which switch from using mostly the autophagosome in quiescence to rely on the ubiquitin-proteasome system (UPS) when proliferating. We aim to find the links between systemic signals, proteostasis and the regulation of aNSC quiescence.
To tackle this question, we have generated an in vitro system that recapitulates the preferential use of autophagy in quiescent and of the UPS in proliferating aNSCs. This gives us a unique opportunity to explore the mechanisms by which proteins are targeted to one or the other system for degradation and to understand how these general processes regulate neurogenesis.
Iván Crespo Enríquez
Targeted Protein Degradation related publications by Group Urbán
- 2019 Quiescence of Adult Mammalian Neural Stem Cells: A Highly Regulated Rest Neuron Go to publication →
- 2019 Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells eLife Go to publication →
- 2016 Return to quiescence of mouse neural stem cells by degradation of a proactivation protein Science Go to publication →