P-glycoprotein and 'lipid rafts': some ambiguous mutual relationships (floating on them, building them or meeting them by chance?).
P-glycoprotein (P-gp) is an active membrane transporter responsible for cell detoxification against numerous amphiphilic compounds, leading to multidrug resistance in tumor cells. It displays entangled connections with its membrane environment since it recognizes its substrates within the cytosolic leaflet and it also translocates some endogenous lipids to the exoplasmic leaflet. Regarding its relationships with membrane microdomains, 'lipid rafts', a literature analysis concludes that (i) P-gp also exists in rafts and non-raft membrane domains, depending on the cell considered, the experimental conditions and the method used to test it; (ii) cholesterol has a positive influence on P-gp function, and this may be a direct effect of the free cholesterol present in membrane or an indirect effect mediated by the cholesterol-enriched microdomains; (iii) when present in rafts, P-gp interacts with protein partners regulating its activity; (iv) P-gp is a lipid translocase that handles the raft-constituting lipids with particular efficiency, and it also influences membrane trafficking in the cell.
Orlowski
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Service de Biophysique des Fonctions Membranaires, Département de Biologie Joliot-Curie, URA 2096 CNRS, CEA Saclay, 91191, Gif-sur-Yvette cedex, France. orlowski@dsvidf.cea.fr
Martin
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Escargueil
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism / Q000502:physiology*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D051242:Caveolin 1 / Q000378:metabolism; D021961:Cell Membrane Structures / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism / Q000502:physiology; D004705:Endocytosis / Q000502:physiology; D006028:Glycosphingolipids / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D017433:Protein Structure, Secondary; D015398:Signal Transduction; D014777:Virus Diseases / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051242:Caveolin 1; D006028:Glycosphingolipids; D008055:Lipids; D002784:Cholesterol; D000251:Adenosine Triphosphatases