FEBS Letters
Volume 582, Issue 30 , Pages 4153-4157, 24 December 2008

Cholesterol but not association with detergent resistant membranes is necessary for the transport function of MRP2/ABCC2

Edited by Sandro Sonnino

Department of Cell Biology, Section Membrane Cell Biology, University Medical Center Groningen, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands

Received 10 October 2008; received in revised form 11 November 2008; accepted 11 November 2008. published online 26 November 2008.

Abstract 

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.

Keywords: ABCC2, HepG2, Raft, Triton X-100 insoluble fraction, Detergent resistant membrane

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PII: S0014-5793(08)00921-6

doi:10.1016/j.febslet.2008.11.013

FEBS Letters
Volume 582, Issue 30 , Pages 4153-4157, 24 December 2008