Broad Sensitivity of Saccharomyces cerevisiae Lacking Ribosome-Associated Chaperone Ssb or Zuo1 to Cations, Including Aminoglycosides

The Hsp70 Ssb and J protein Zuo1 of Saccharomyces cerevisiae are ribosome-associated molecular chaperones, proposed to be involved in the folding of newly synthesized polypeptide chains. Cells lacking Ssb and/or Zuo1 have been reported to be hypersensitive to cationic aminoglycoside protein synthesis inhibitors that affect translational fidelity and to NaCl. Since we found that Deltassb1 Deltassb2 (Deltassb1,2), Deltazuo1, and wild-type cells have very similar levels of translational misreading in the absence of aminoglycosides, we asked whether the sensitivities to aminoglycosides and NaCl represent a general increase in sensitivity to cations. We found that Deltassb1,2 and Deltazuo1 cells are hypersensitive to a wide range of cations. This broad sensitivity is similar to that of cells having lowered activity of major plasma membrane transporters, such as the major K+ transporters Trk1 and Trk2 or their regulators Hal4 and Hal5. Like Deltahal4,5 cells, Deltassb1,2 and Deltazuo1 cells have increased intracellular levels of Na+ and Li+ upon challenge with higher-than-normal levels of these cations, due to an increased rate of influx. In the presence of aminoglycosides, Deltassb1,2, Deltazuo1, and Deltahal 4,5 cells have similarly increased levels of translational misreading. We conclude that, in vivo, the major cause of the aminoglycoside sensitivity of cells lacking ribosome-associated molecular chaperones is a general increase in cation influx, perhaps due to altered maturation of membrane proteins.