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Purification of Hsp104, a Protein Disaggregase
Published on: September 30, 2011
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Stress-induced protein disaggregation in the endoplasmic reticulum catalysed by BiP
Eduardo Pinho Melo1,2, Tasuku Konno3, Ilaria Farace3
1Department of Clinical Neurosciences, UK Dementia Research Institute, University of Cambridge, Cambridge, UK. emelo@ualg.pt.
Nature Communications
|May 6, 2022
Summary
The Endoplasmic Reticulum (ER) possesses a system to resolve protein aggregates, crucial for cellular proteostasis. This disaggregation activity is mediated by the molecular chaperone BiP during ER stress.
Area of Science:
- Cellular Biology
- Neuroscience
- Biochemistry
Background:
- Protein synthesis occurs in the Endoplasmic Reticulum (ER), where proper folding is essential.
- Misfolded proteins can aggregate, contributing to diseases like neurodegeneration.
- Cytoplasmic machinery can resolve protein aggregates, but ER-based systems are poorly understood.
Purpose of the Study:
- To investigate whether the ER possesses a disaggregation system analogous to the cytoplasm.
- To identify the mechanisms involved in resolving protein aggregates within the ER.
Main Methods:
- Developed a novel protein aggregation probing system with sub-organellar resolution.
- Utilized mammalian cell types, including neurons, for experiments.
- Applied pharmacological induction of ER stress and analyzed aggregate clearance.
Main Results:
- Observed steady-state protein aggregate accumulation in the ER.
- ER stress induction stimulated, rather than augmented, aggregate clearance.
- Demonstrated that the molecular chaperone BiP catalyzes this ER disaggregation activity.
Conclusions:
- The ER has a previously unknown capability to resolve protein aggregates under stress.
- This ER disaggregation system is mediated by the stress-responsive chaperone BiP.
- This represents a non-redundant component of the proteostasis-restorative ER stress response.
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