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Cholesterol but not association with detergent resistant membranes is necessary for the transport function of MRP2/ABCC2
Author(s) -
Ito Kousei,
Hoekstra Dick,
van IJzendoorn Sven C.D.
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.11.013
Subject(s) - multidrug resistance associated protein 2 , cholesterol , chemistry , membrane , amphiphile , efflux , function (biology) , transporter , biochemistry , atp binding cassette transporter , biology , microbiology and biotechnology , organic chemistry , copolymer , gene , polymer
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.