De novo [PSI ⁺] prion formation involves multiple pathways to form infectious oligomers

Area of Science:

• Neurodegenerative diseases
• Protein misfolding
• Yeast prions

Background:

• Prion and other neurodegenerative diseases involve misfolded protein assemblies called amyloids.
• Mechanisms of amyloid transmission are being uncovered, but in vivo formation remains unclear.

Purpose of the Study:

• To investigate the early steps of amyloid formation in vivo using the yeast prion [PSI+].
• To understand the complexity of de novo [PSI+] induction.

Main Methods:

• Utilized 4D live cell imaging to observe de novo induction of [PSI+].
• Performed biochemical analysis of de novo induced yeast cultures.
• Assessed the conversion ability of newly formed oligomers.

Main Results:

• Identified four distinct pathways for the formation of fluorescent structures during de novo [PSI+] induction.
• Observed that newly formed SDS-resistant prion oligomers change in size over time.
• Demonstrated that lysates from de novo induced cultures can convert [psi-] cells to [PSI+] cells.

Conclusions:

• De novo prion induction is more complex than previously understood.
• Newly formed prion oligomers exhibit infectious properties, capable of seeding new prion formations.