Hsp70 chaperones, Ssa1 and Ssa2, limit poly(A) binding protein aggregation.
Hannah E Buchholz1, Sean A Martin1, Jane E Dorweiler1
1Department of Biological Sciences, Marquette University, Milwaukee, WI 53201-1881.
Molecular Biology of the Cell
|April 9, 2025
Summary
Loss of Hsp70 chaperones in yeast causes endogenous Pab1 protein aggregation. Overexpressing other chaperones like Hsp104 and Sis1 can prevent this, suggesting Hsp70
Area of Science:
- Cellular Biology
- Protein Homeostasis
- Molecular Chaperones
Background:
- Hsp70 chaperones are crucial for protein folding and preventing aggregation.
- Yeast lacking Ssa1 and Ssa2 Hsp70s exhibit reduced growth and lifespan.
- The behavior of endogenous proteins in Hsp70-deficient cells is not well understood.
Purpose of the Study:
- To investigate the aggregation of endogenous wild-type Poly A binding protein (Pab1) in yeast with limited Hsp70.
- To determine if other chaperones can compensate for Hsp70 deficiency.
- To understand the role of Hsp70 in age-related protein aggregation.
Main Methods:
- Utilized yeast strains deficient in Ssa1 and Ssa2 Hsp70 proteins.
- Observed the formation of large Pab1 inclusions under normal and heat shock conditions.
- Assessed the effect of overexpressing Ssa1, Hsp104, and Sis1 on Pab1 aggregation.
- Analyzed stress granule dynamics in the presence of Pab1 inclusions.
Main Results:
- Wild-type Pab1 forms large cytoplasmic inclusions in approximately half of ssa1Δssa2Δ yeast cells without stress.
- Overexpression of Ssa1, Hsp104, or Sis1 significantly reduces Pab1 inclusion formation.
- Stress granules form independently of Pab1 inclusions, but co-occurrence slows disassembly.
- Pab1 inclusions also form in saturated wild-type cultures and can be partially rescued by Ssa1 overexpression.
Conclusions:
- Hsp70 chaperones limit endogenous protein aggregation in healthy cells.
- Depletion of active Hsp70 may drive age-related protein aggregation.
- Other chaperones like Hsp104 and Sis1 can partially compensate for Hsp70 loss.
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