title: Clearance of yeast prions by misfolded multi-transmembrane proteins.
abstract: Accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces the stress response to protect cells against toxicity by the unfolded protein response (UPR), heat shock response (HSR), and ER-associated degradation pathways. Here, we found that over-production of C-terminally truncated multi-transmembrane (MTM) mutant proteins triggers HSR, but not UPR, and clearance of yeast prions [PSI(+)] and [URE3]. One of the mutant MTM proteins, Dip5ΔC-v82, produces a disabled amino-acid permease. Fluorescence microscopy analysis revealed abnormal accumulation of Dip5ΔC-v82 in the ER. Importantly, the mutant defective in the GET pathway, which functions for ER membrane insertion of tail-anchored proteins, failed to translocate Dip5ΔC-v82 to the ER and disabled Dip5ΔC-v82-mediated prion clearance. These findings suggest that the GET pathway plays a pivotal role in quality assurance of MTM proteins, and entraps misfolded MTM proteins into ER compartments, leading to loss-of-prion through a yet undefined mechanism.
authors: Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Tokyo 108-8639, Japan.
authors: Chie
authors: C
authors: Arai
authors: Hiroshi
authors: H
authors: Kurahashi
authors: Masao
authors: M
authors: Ishiwata
authors: Keita
authors: K
authors: Oishi
authors: Yoshikazu
authors: Y
authors: Nakamura
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism; D060746:Endoplasmic Reticulum-Associated Degradation / Q000502:physiology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010454:Peptide Termination Factors / Q000378:metabolism*; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011328:Prions / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D056811:Unfolded Protein Response / Q000502:physiology*; D015003:Yeasts / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae