Transcriptome analyses of pdr5Dyor1D mutant in yeasts

ABSTRACT: ATP-binding cassette transporters Pdr5 and Yor1 from Saccharomyces cerevisiae control the asymmetric distribution of phospholipids across the plasma membrane as well as serving as ATP-dependent drug efflux pumps. Mutant strains lacking these transporter proteins were found to exhibit very different resistant phenotypes to two inhibitors of sphingolipid biosynthesis that act either late (aureobasidin A:AbA) or early (myriocin: Myr) in the pathway leading to production of these important plasma membrane lipids. These pdr5D yor1 strains were highly AbA resistant but extremely sensitive to Myr. We provide evidence that these phenotypic changes are likely due to modulation of the plasma membrane flippase complexes: Dnf1/Lem3 and Dnf2/Lem3. Flippases act to move phospholipids from the outer to the inner leaflet of the plasma membrane. Genetic analyses indicate that lem3D mutant strains are highly AbA sensitive and Myr resistant. These phenotypes are fully epistatic to those seen in pdr5D yor1 strains. Direct analysis of AbA-induced signaling demonstrated that loss of Pdr5 and Yor1 inhibited the AbA-triggered phosphorylation of the AGC kinase Ypk1 and its substrate Orm1. Microarray experiments found that a pdr5D yor1 strain induced a Pdr1-dependent induction of the entire Pdr regulon. Our data support the view that Pdr5/Yor1 negatively regulate flippase function and activity of the nuclear Pdr1 transcription factor. Together, these data argue that the interaction of the ABC transporters Pdr5 and Yor1 with the Lem3-dependent flippases regulate permeability of AbA via control of plasma membrane protein function as seen for the high-affinity tryptophan permease Tat2. the transcriptome of pdr5Dyor1D double mutants was compared either to wild type cells or to pdr5Dyor1Dpdr1D triple mutant.

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: frederic devaux 

PROVIDER: E-GEOD-65264 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress