Cellular and Molecular Life Sciences CMLS

, Volume 63, Issue 9, pp 1038–1059

P-glycoprotein and ‘lipid rafts’: some ambiguous mutual relationships (floating on them, building them or meeting them by chance?)

Review

DOI: 10.1007/s00018-005-5554-9

Cite this article as:
Orlowski, S., Martin, S. & Escargueil, A. Cell. Mol. Life Sci. (2006) 63: 1038. doi:10.1007/s00018-005-5554-9

Abstract.

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.

Keywords.

P-glycoprotein multidrug resistance drug transport lipid translocase cholesterol sphingolipids lipid rafts lipid traffic 

Copyright information

© Birkhäuser Verlag, Basel 2006

Authors and Affiliations

  1. 1.Service de Biophysique des Fonctions Membranaires, Département de Biologie Joliot-CurieURA 2096 CNRSGif-sur-Yvette cedexFrance
  2. 2.Group of Biology and Pharmacogenetics of Human Tumors, INSERM U673Hôpital Saint-Antoine et Université Pierre et Marie CurieParisFrance

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