J Proteins Counteract Amyloid Propagation and Toxicity in Yeast

Abstract

The accumulation of misfolded proteins as amyloids is associated with pathology in dozens of debilitating human disorders, including diabetes, Alzheimer’s, Parkinson’s, and Huntington’s diseases. Expressing human amyloid-forming proteins in yeast is toxic, and yeast prions that propagate as infectious amyloid forms of cellular proteins are also harmful. The yeast system, which has been useful for studying amyloids and their toxic effects, has provided much insight into how amyloids affect cells and how cells respond to them. Given that an amyloid is a protein folding problem, it is unsurprising that the factors found to counteract the propagation or toxicity of amyloids in yeast involve protein quality control. Here, we discuss such factors with an emphasis on J-domain proteins (JDPs), which are the most highly abundant and diverse regulators of Hsp70 chaperones. The anti-amyloid effects of JDPs can be direct or require interaction with Hsp70.

How Big Is the Yeast Prion Universe?

“…Hsp104 is a disaggregation-stimulating protein essential for propagation of [PSI + ] [40] and most other yeast prions (reviewed in [21,22,41]). Many of the chaperones and different factors required for the propagation of yeast prions have been described and discussed in recent reviews [14,42,43], for these reasons they will not be discussed here. NM-domain forms reversible pH-dependent biomolecular condensates [44].…”