Neuronal differentiation remodels the cellular chaperome
Abstract/Contents
- Abstract
- Neural stem and progenitor cells (NSPCs) are critical for continued cellular replacement in the adult brain. Life-long maintenance of a functional NSPC pool necessitates stringent mechanisms to preserve a pristine proteome. We find that the NSPCs chaperone network robustly maintains misfolded protein solubility and stress resilience through high levels of ATP-dependent chaperonin TRiC/CCT. Strikingly, NSPC differentiation rewires the chaperone network, reducing TRiC/CCT levels and inducing ATP-independent small HSPs. This switches the proteostasis strategy in neural progeny cells to promote sequestration of misfolded protein into protective inclusions. The chaperone network of NSPCs is more effective than that of differentiated cells, leading to their improved management of proteotoxic stress and amyloidogenic proteins. However, NSPC proteostasis is impaired by brain aging. The less efficient chaperone network of differentiated neural progeny may contribute to their susceptibility to neurodegenerative diseases characterized by aberrant protein misfolding and aggregation.
Description
| Type of resource | software, multimedia |
|---|---|
| Date created | 2019 |
Creators/Contributors
| Author | Vonk, Willianne |
|---|---|
| Author | Rainbolt, T. Kelly |
| Author | Webb, Ashley E. |
| Author | Brunet, Anne |
| Contributing author | Dolan, Patrick |
| Principal investigator | Frydman, Judith |
Subjects
| Subject | neural development |
|---|---|
| Subject | protein homeostasis |
| Subject | protein folding |
| Subject | proteostasis |
| Subject | chaperonin |
| Subject | TRiC |
| Subject | chaperone |
| Genre | Dataset |
Bibliographic information
| Related item | |
|---|---|
| Location | https://purl.stanford.edu/gd935jm2479 |
Access conditions
- Use and reproduction
- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
Preferred citation
- Preferred Citation
- Willianne Vonk and T. Kelly Rainbolt and Ashley E. Webb and Anne Brunet and Judith Frydman and Patrick Dolan. (2019). Neuronal differentiation remodels the cellular chaperome. Stanford Digital Repository. Available at: https://purl.stanford.edu/gd935jm2479
Collection
Stanford Research Data
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- Contact
- jfrydman@stanford.edu
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