Are lipid rafts involved in ABC transporter-mediated drug resistance of tumor cells?

Since their discovery, lipid rafts have been implicated in several cellular functions, including protein transport in polarized cells and signal transduction. Also in multidrug resistance lipid rafts may be important with regard to the localization of ATP-binding cassette (ABC) transporters in these membrane domains. This specific localization may support the activity of these ABC transporters as drug efflux pumps and this raises important questions regarding the dependence on lipid raft constituents. In this respect, two lipid classes immediately come into play, as both sphingolipids and sterols are generally assumed to be important in the generation and maintenance of lipid rafts. Apart from lateral interactions with lipids in the membrane bilayer, one can also envision that transverse interactions with respect to the membrane bilayer play a role in positioning and function of ABC transporters. Indeed, some evidence exists for a role of the actin cytoskeleton in stabilizing the position of ABC transporters in a certain membrane area. ABC transporters may be directly linked to the actin cytoskeleton, or indirectly via lipid rafts. In this review, we will evaluate whether ABC transporters are dependent on a particular membrane environment for their function and which of the lipid raft constituents appear to be essential for this dependency.