Vba4p, a vacuolar membrane protein, is involved in the drug resistance and vacuolar morphology of Saccharomyces cerevisiae

Abstract

In the vacuolar basic amino acid (VBA) transporter family of Saccharomyces cerevisiae, VBA4 encodes a vacuolar membrane protein with 14 putative transmembrane helices. Transport experiments with isolated vacuolar membrane vesicles and estimation of the amino acid contents in vacuoles showed that Vba4p is not likely involved in the transport of amino acids. We found that the vba4Δ cells, as well as vba1Δ and vba2Δ cells, showed increased susceptibility to several drugs, particularly to azoles. Although disruption of the VBA4 gene did not affect the salt tolerance of the cells, vacuolar fragmentation observed under high salt conditions was less prominent in vba4Δ cells than in wild type, vba1Δ, and vba2Δ cells. Vba4p differs from Vba1p and Vba2p as a vacuolar transporter but is important for the drug resistance and vacuolar morphology of S. cerevisiae.

Graphical abstract

Vba4p is a vacuolar membrane protein in the VBA transporter family of Saccharomyces cerevisiae (A). Disruption of VBA4 resulted in increased susceptibility to azoles (B).

Key words:

• vacuolar transporter
• azole
• multidrug resistance

Acknowledgments

This work was supported in part by the Public Foundation of Elizabeth Arnold-Fuji (to M.K-K.); JSPS KAKENHI grant numbers [15H04486 (to Y.K.)], [15K07396 (to T.S.)]. P. Pongcharoen is a recipient of a scholarship from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.