Stress-dependent proteolytic processing of the actin assembly protein Lsb1 modulates a yeast prion

Area of Science:

• Molecular Biology
• Cell Biology
• Prion Biology

Background:

• Yeast prions, like [PSI(+)], are amyloid aggregates of Q/N-rich proteins, serving as models for mammalian amyloidoses.
• Prion propagation relies on cellular chaperones, ubiquitin proteolysis, and the actin cytoskeleton, especially during stress recovery.
• Lsb1 and Lsb2 proteins interact with the actin assembly protein Las17 and are involved in the endocytic pathway.

Purpose of the Study:

• To investigate the role of Lsb1 in the maintenance of the yeast Sup35 prion during and after heat shock.
• To elucidate the regulatory mechanisms controlling Lsb1 function in protein aggregate partitioning under stress conditions.

Main Methods:

• Experimental manipulation of yeast strains to assess prion maintenance under heat shock.
• Analysis of Lsb1 protein abundance, localization, and regulation by ubiquitination and proteolytic processing.
• Investigating the role of the Guided Entry of Tail-anchored proteins pathway in Lsb1 regulation.

Main Results:

• Lsb1, similar to Lsb2, was found to regulate the maintenance of the Sup35 prion during and after heat shock.
• Lsb1 abundance and its cycling between cellular compartments are controlled by the Guided Entry of Tail-anchored proteins pathway and Rsp5-dependent ubiquitination.
• Heat shock-induced proteolytic processing of Lsb1 is essential for prion maintenance under stress.

Conclusions:

• Lsb proteins are involved in the partitioning of protein aggregates within stressed yeast cells.
• Lsb1 is identified as a novel component of a regulated pathway controlling protein aggregation in response to environmental changes.
• These findings contribute to understanding the cellular mechanisms governing prion stability and protein homeostasis during stress.