The ART-Rsp5 Ubiquitin Ligase Network Comprises a Plasma Membrane Quality Control System That Protects Yeast Cells From Proteotoxic Stress

Elife. 2013 Apr 16;2:e00459. doi: 10.7554/eLife.00459.

Abstract

Secretory cargo that cannot fold properly in the ER are selectively targeted for removal by a well-studied ER-associated degradation pathway, or ERAD. In contrast, very little is known about post-ER quality control mechanisms for damaged or misfolded integral membrane proteins. Here we describe a quality control function of the Rsp5-ART ubiquitin ligase adaptor network that functions to protect plasma membrane (PM) integrity. Failure to mediate this protective response during heat stress leads to toxic accumulation of misfolded integral membrane proteins at the cell surface, which causes loss of PM integrity and cell death. Thus, the Rsp5-ART network comprises a PM quality control system that works together with sequential quality control pathways in the ER and Golgi to (i) target the degradation of proteins that have exceeded their functional lifetime due to damage and/or misfolding and (ii) limit the toxic accumulation of specific proteins at the cell surface during proteotoxic stress. DOI:http://dx.doi.org/10.7554/eLife.00459.001.

Keywords: S. cerevisiae; endocytosis; membrane traffic; proteostasis; quality control; ubiquitin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Membrane / enzymology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Endocytosis
  • Endoplasmic Reticulum / enzymology*
  • Endoplasmic Reticulum-Associated Degradation
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Golgi Apparatus / enzymology*
  • Heat-Shock Response
  • Hot Temperature
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Protein Denaturation
  • Protein Folding
  • Protein Transport
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Stress, Physiological*
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Ubiquitin-Protein Ligase Complexes / genetics
  • Ubiquitin-Protein Ligase Complexes / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Membrane Proteins
  • SWI4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Ubiquitin-Protein Ligase Complexes
  • RSP5 protein, S cerevisiae