Xenobiotic Transporter-Adaptor Network

Abstract

  Many types of xenobiotic transporters have been identified. They generally exhibit multispecific recognition of various types of substrates, and mediate membrane permeation of therapeutic agents, thereby playing important roles in drug absorption and disposition. It has recently been proposed that protein-protein interactions involving the xenobiotic transporters may affect their function, localization and expression on plasma membranes. So-called adaptor proteins that directly interact with the transporters include PDZ domain-containing proteins (PSD95, Dlg and ZO1). These PDZ adaptors have multiple PDZ domains in their structure, and each PDZ domain can interact with the cytosolic region of the transporters, and so it has been hypothesized that transporters are localized within networks consisting of several transporters and adaptors. Interaction with a PDZ adaptor is essential for the cell-surface localization of at least some xenobiotic transporters, and therefore, such interaction could be required for efficiency and fidelity in the vectorial transport of xenobiotics and therapeutic agents in epithelial cells. This review article summarizes recent evidence on the interactions of xenobiotic transporters with adaptor proteins, and presents a working hypothesis concerning their pharmacological significance.