Author(s)
Danny Hatters
Published 4 Projects
Metabolism Biochemistry Cell Biology Protein Aggregation Proteasome
Content
Video Abstract (AI generated) (01:16) Paper Preprint (zenodo,"")An extensive network of chaperones and other proteins maintain protein homeostasis and guard against inappropriate protein aggregation that is a hallmark of neurodegenerative diseases. Using a fluorescence resonance energy-based biosensor that simultaneously reports on intact cellular chaperone holdase activity and detrimental aggregation propensity, we investigated the buffering capacity of the systems managing protein homeostasis in the nucleus of the human cell line HEK293 compared to the cytosol. We found that the nucleus showed lower net holdase activity and reduced capacity to suppress protein aggregation, suggesting that the nuclear quality control resources are less effective compared to those in the cytosol. Aggregation of mutant huntingtin exon 1 protein (Httex1) in the cytosol appeared to deplete cytosolic chaperone supply by depleting holdase activity. Unexpectedly, the same stress increased holdase activity in the nucleus suggesting that proteostasis stress can trigger a rebalance of chaperone supply in different subcellular compartments. Collectively the findings suggest the cytosol has more capacity to manage imbalances in proteome foldedness than the nucleus, but chaperone supply can be redirected into the nucleus under conditions of proteostasis stress caused by cytosolic protein aggregation.
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Danny Hatters. (2021, Nov 1).A biosensor to gauge protein homeostasis resilience differences in the nucleus compared to cytosol of mammalian cells[Video]. Scitok. https://scitok.com/project/p/1cafddde
B. Raeburn Candice. "A biosensor to gauge protein homeostasis resilience differences in the nucleus compared to cytosol of mammalian cells" Scitok, uploaded by Hatters Danny, 1 Nov, 2021, https://scitok.com/project/p1cafddde
Danny Hatters. "A biosensor to gauge protein homeostasis resilience differences in the nucleus compared to cytosol of mammalian cells" Scitok. (Nov 1, 2021). https://scitok.com/project/p/1cafddde
Danny Hatters (Nov 1, 2021). A biosensor to gauge protein homeostasis resilience differences in the nucleus compared to cytosol of mammalian cells Scitok. https://scitok.com/project/p/1cafddde
Danny Hatters. A biosensor to gauge protein homeostasis resilience differences in the nucleus compared to cytosol of mammalian cells[video]. 2021 Nov 1. https://scitok.com/project/p/1cafddde
@online{al2006link, title={ A biosensor to gauge protein homeostasis resilience differences in the nucleus compared to cytosol of mammalian cells }, author={ Hatters, Danny }, organization={Scitok}, month={ Nov }, day={ 1 }, year={ 2021 }, url = {https://scitok.com/project/p/1cafddde}, }