Lipid dependence of ABC transporter localization and function.
Lipid rafts have been implicated in many cellular functions, including protein and lipid transport and signal transduction. ATP-binding cassette (ABC) transporters have also been localized in these membrane domains. In this review the evidence for this specific localization will be evaluated and discussed in terms of relevance to ABC transporter function. We will focus on three ABC transporters of the A, B and C subfamily, respectively. Two of these transporters are relevant to multidrug resistance in tumor cells (Pgp/ABCB1 and MRP1/ABCC1), while the third (ABCA1) is extensively studied in relation to the reverse cholesterol pathway and cellular cholesterol homeostasis. We will attempt to derive a generalized model of lipid rafts to which they associate based on the use of various different lipid raft isolation procedures. In the context of lipid rafts, modulation of ABC transporter localization and function by two relevant lipid classes, i.e. sphingolipids and cholesterol, will be discussed.
Klappe
Karin
K
Department of Cell Biology, Section Membrane Cell Biology, University Medical Center Groningen, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Hummel
Ina
I
Hoekstra
Dick
D
Kok
Jan Willem
JW
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D021962:Membrane Microdomains / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism / Q000502:physiology*; D013107:Sphingolipids / Q000502:physiology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D002784:Cholesterol; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013107:Sphingolipids