A non-Q/N-rich prion domain of a foreign prion, [Het-s], can propagate as a prion in yeast

Vibha Taneja1, Marie-Lise Maddelein, Nicolas Talarek

  • 1Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.

Molecular Cell
|July 7, 2007
PubMed

Insights

Fungal prion proteins, HET-s, can propagate in yeast, a foreign host, even without Q/N-rich regions. These yeast-propagated prions are infectious in their native fungal host.

Area of Science:

  • Protein misfolding and aggregation
  • Prion biology
  • Fungal genetics

Background:

  • Prions are infectious proteins causing neurodegenerative diseases.
  • Yeast prions typically require Q/N-rich domains for propagation.
  • Fungal prion proteins like HET-s lack these Q/N-rich regions.

Purpose of the Study:

  • To investigate if non-Q/N-rich fungal prions can propagate in yeast.
  • To determine if yeast-hosted fungal prions retain infectivity.
  • To explore interactions between different prion types.

Main Methods:

  • Fusion of the HET-s prion domain to Green Fluorescent Protein (GFP).
  • Transient overexpression in yeast to induce prion formation.
  • Analysis of aggregate morphology (ring-like and dot structures).
  • Assessing dependence on the Hsp104 chaperone.
  • Testing infectivity of yeast-propagated prions in Podospora.

Main Results:

  • HET-s-GFP fusion protein successfully propagated as a prion in yeast.
  • Propagation involved ring-like aggregates upon induction and dot aggregates in daughter cells.
  • Dot propagation, but not ring formation, required the Hsp104 chaperone.
  • [PIN(+)] yeast prion enhanced HET-s ring formation, indicating cross-prion interaction.
  • HET-s aggregates propagated in yeast were infectious in Podospora.

Conclusions:

  • Yeast can host prions lacking Q/N-rich domains, expanding the known host range for prions.
  • Prions with and without Q/N-rich regions can interact within the same cell.
  • This study demonstrates prion propagation in a heterologous host and suggests the potential existence of native non-Q/N-rich yeast prions.

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