Control of Plasma Membrane Permeability by ABC Transporters.

摘要: ATP-binding cassette transporters Pdr5 and Yor1 from Saccharomyces cerevisiae control the asymmetric distribution of phospholipids across plasma membrane as well serving ATP-dependent drug efflux pumps. Mutant strains lacking these transporter proteins were found to exhibit very different resistance phenotypes two inhibitors sphingolipid biosynthesis that act either late (aureobasidin A [AbA]) or early (myriocin [Myr]) in pathway leading production important lipids. These pdr5Δ yor1 highly AbA resistant but extremely sensitive Myr. We provide evidence phenotypic changes are likely due modulation flippase complexes, Dnf1/Lem3 Dnf2/Lem3. Flippases move outer inner leaflet membrane. Genetic analyses indicate lem3Δ mutant Myr resistant. fully epistatic those seen strains. Direct analysis AbA-induced signaling demonstrated loss inhibited AbA-triggered phosphorylation AGC kinase Ypk1 its substrate Orm1. Microarray experiments a strain induced Pdr1-dependent induction entire Pdr regulon. Our data support view Pdr5/Yor1 negatively regulate function activity nuclear Pdr1 transcription factor. Together, argue interaction ABC with Lem3-dependent flippases regulates permeability via protein for high-affinity tryptophan permease Tat2.