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

Kousei Ito; Dick Hoekstra; Sven C. D. van IJzendoorn

doi:10.1016/j.febslet.2008.11.013

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

Kousei Ito, Dick Hoekstra, Sven C. D. van IJzendoorn^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

8 Citations (Scopus)

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. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

Original language	English
Pages (from-to)	4153-4157
Number of pages	5
Journal	FEBS Letters
Volume	582
Issue number	30
DOIs	https://doi.org/10.1016/j.febslet.2008.11.013
Publication status	Published - 24-Dec-2008

Keywords

ABCC2
HepG2
Raft
Triton X-100 insoluble fraction
Detergent resistant membrane
TAUROURSODEOXYCHOLIC ACID INSERTS
CHOLESTATIC RAT-LIVER
P-GLYCOPROTEIN
CANALICULAR MEMBRANES
LIPID MICRODOMAINS
DRUG-RESISTANCE
EXPORT PUMP
MRP2
PROTEINS
CELLS

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@article{89b4af20816c4bf5860a25d7356529c2,

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

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. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.",

keywords = "ABCC2, HepG2, Raft, Triton X-100 insoluble fraction, Detergent resistant membrane, TAUROURSODEOXYCHOLIC ACID INSERTS, CHOLESTATIC RAT-LIVER, P-GLYCOPROTEIN, CANALICULAR MEMBRANES, LIPID MICRODOMAINS, DRUG-RESISTANCE, EXPORT PUMP, MRP2, PROTEINS, CELLS",

author = "Kousei Ito and Dick Hoekstra and {van IJzendoorn}, {Sven C. D.}",

year = "2008",

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day = "24",

doi = "10.1016/j.febslet.2008.11.013",

language = "English",

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journal = "FEBS Letters",

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T1 - Cholesterol but not association with detergent resistant membranes is necessary for the transport function of MRP2/ABCC2

AU - Ito, Kousei

AU - Hoekstra, Dick

AU - van IJzendoorn, Sven C. D.

PY - 2008/12/24

Y1 - 2008/12/24

N2 - 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. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

AB - 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. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

KW - ABCC2

KW - HepG2

KW - Raft

KW - Triton X-100 insoluble fraction

KW - Detergent resistant membrane

KW - TAUROURSODEOXYCHOLIC ACID INSERTS

KW - CHOLESTATIC RAT-LIVER

KW - P-GLYCOPROTEIN

KW - CANALICULAR MEMBRANES

KW - LIPID MICRODOMAINS

KW - DRUG-RESISTANCE

KW - EXPORT PUMP

KW - MRP2

KW - PROTEINS

KW - CELLS

U2 - 10.1016/j.febslet.2008.11.013

DO - 10.1016/j.febslet.2008.11.013

M3 - Article

SN - 0014-5793

VL - 582

SP - 4153

EP - 4157

JO - FEBS Letters

JF - FEBS Letters

IS - 30

ER -