Normal levels of the antiprion proteins Btn2 and Cur1 cure most newly formed [URE3] prion variants

Proc Natl Acad Sci U S A. 2014 Jul 1;111(26):E2711-20. doi: 10.1073/pnas.1409582111. Epub 2014 Jun 17.

Abstract

[URE3] is an amyloid prion of the Saccharomyces cerevisiae Ure2p, a regulator of nitrogen catabolism. Overproduction of Btn2p, involved in late endosome to Golgi protein transport, or its paralog Cur1p, cures [URE3]. Btn2p, in curing, is colocalized with Ure2p in a single locus, suggesting sequestration of Ure2p amyloid filaments. We find that most [URE3] variants generated in a btn2 cur1 double mutant are cured by restoring normal levels of Btn2p and Cur1p, with both proteins needed for efficient curing. The [URE3] variants cured by normal levels of Btn2p and Cur1p all have low seed number, again suggesting a seed sequestration mechanism. Hsp42 overproduction also cures [URE3], and Hsp42p aids Btn2 overproduction curing. Cur1p is needed for Hsp42 overproduction curing of [URE3], but neither Btn2p nor Cur1p is needed for overproduction curing by the other. Although hsp42Δ strains stably propagate [URE3-1], hsp26Δ destabilizes this prion. Thus, Btn2p and Cur1p are antiprion system components at their normal levels, acting with Hsp42. Btn2p is related in sequence to human Hook proteins, involved in aggresome formation and other transport activities.

Keywords: Bmh1; Sis1; prion seed sequestration.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Transport Systems / genetics
  • Amino Acid Transport Systems / metabolism*
  • Gene Expression Regulation, Fungal / genetics*
  • Gene Knockout Techniques
  • Glutathione Peroxidase / genetics*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Plasmids / genetics
  • Prions / genetics*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Amino Acid Transport Systems
  • BTN2 protein, S cerevisiae
  • CUR1 protein, S cerevisiae
  • HSP42 protein, S cerevisiae
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Prions
  • Saccharomyces cerevisiae Proteins
  • Glutathione Peroxidase
  • URE2 protein, S cerevisiae