Dispersion of Endoplasmic Reticulum-associated Compartments by 4-phenyl Butyric Acid in Yeast Cells

Cell Struct Funct. 2019 Nov 23;44(2):173-182. doi: 10.1247/csf.19023. Epub 2019 Oct 17.

Abstract

In yeast Saccharomyces cerevisiae cells, some aberrant multimembrane-spanning proteins are not transported to the cell surface but form and are accumulated in endoplasmic reticulum (ER)-derived subcompartments, known as the ER-associated compartments (ERACs), which are observed as puncta under fluorescence microscopy. Here we show that a mutant of the cell surface protein Pma1, Pma1-2308, was accumulated in the ERACs, as well as the heterologously expressed mammalian cystic fibrosis transmembrane conductance regulator (CFTR), in yeast cells. Pma1-2308 and CFTR were located on the same ERACs. We also note that treatment of cells with 4-phenyl butyric acid (4-PBA) compromised the ERAC formation by Pma1-2308 and CFTR, suggesting that 4-PBA exerts a chaperone-like function in yeast cells. Intriguingly, unlike ER stress induced by the canonical ER stressor tunicamycin, ER stress that was induced by Pma1-2308 was aggravated by 4-PBA. We assume that this observation demonstrates a beneficial aspect of ERACs, and thus propose that the ERACs are formed through aggregation of aberrant transmembrane proteins and work as the accumulation sites of multiple ERAC-forming proteins for their sequestration.Key words: protein aggregation, organelle, unfolded protein response, ER stress, 4-PBA.

Keywords: 4-PBA; ER stress; organelle; protein aggregation; unfolded protein response.

MeSH terms

  • Endoplasmic Reticulum / drug effects*
  • Endoplasmic Reticulum / metabolism
  • Phenylbutyrates / pharmacology*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / metabolism

Substances

  • Phenylbutyrates
  • 4-phenylbutyric acid