Cholesterol but not association with detergent resistant membranes is necessary for the transport function of MRP2/ABCC2.
MRP2(/ABCC2) excretes amphiphilic organic anions into bile, and associates with detergent-resistant bile canalicular membrane domains (DRM). Here, we have evaluated sensitivities of MRP2 transport function and DRM association by titrating the cellular cholesterol content. We demonstrate that the role of cholesterol in the partitioning of MRP2 to DRM can be separated from the role of cholesterol in the function of MRP2, such that (i) cholesterol is not necessary for the polarized distribution of MRP2 at the canalicular membrane, (ii) partitioning into DRM is not required for MRP2 function, yet (iii) the presence of cholesterol is necessary for transport activity.
Ito
Kousei
K
Department of Cell Biology, Section Membrane Cell Biology, University Medical Center Groningen, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Hoekstra
Dick
D
van Ijzendoorn
Sven C D
SC
D001692:Biological Transport; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D003902:Detergents / Q000737:chemistry; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*
D002784:Cholesterol; D003902:Detergents; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human