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High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
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Spatial quality control bypasses cell-based limitations on proteostasis to promote prion curing
Courtney L Klaips1, Megan L Hochstrasser1, Christine R Langlois1
1Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, United States.
Elife
|December 10, 2014
Summary
Thermal stress disassembles Sup35 prions using the Hsp104 chaperone. Cell division limits proteostasis capacity, but spatial engagement of quality control factors can bypass this restriction.
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Homeostasis
Background:
- The proteostasis network maintains protein folding and quality control.
- Protein misfolding and aggregation are implicated in various diseases.
- Cellular limitations on proteostasis capacity are not fully understood.
Purpose of the Study:
- To identify cell-based restrictions on proteostasis capacity.
- To elucidate the mechanism of thermal stress-induced prion curing.
Main Methods:
- Investigated the [PSI(+)]/Sup35 prion system under thermal stress.
- Utilized molecular chaperone Hsp104 for aggregate disassembly analysis.
- Examined Hsp104 activity in relation to cell cycle stage.
Main Results:
- Heat shock disassembles Sup35 amyloid via the Hsp104 chaperone.
- Hsp104 activity is dependent on engagement with non-prion aggregates.
- Asymmetric retention of Hsp104 in late cell-cycle stages enhances its efficacy.
Conclusions:
- Cell division represents a significant limitation on proteostasis capacity.
- Spatial engagement of quality control factors can overcome cellular proteostasis limits.
- Hsp104's mechanism offers insights into managing protein misfolding.
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