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ABCB4 exports phosphatidylcholine in a sphingomyelin-dependent manner
Yu Zhao1, Masato Ishigami2, Kohjiro Nagao1
1Institute for integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8502, Japan.
Journal of Lipid Research
|January 21, 2015
Summary
Sphingomyelin (SM) depletion unexpectedly suppressed phosphatidylcholine (PC) efflux via ABCB4, while stimulating it via ABCA1. ABCB4 requires a SM-rich membrane environment for optimal function.
Area of Science:
- Cell biology
- Lipid metabolism
- Membrane transport
Background:
- ABCB4 protein transports phosphatidylcholine (PC) into bile from the canalicular membrane of hepatocytes.
- Sphingomyelin (SM) depletion is known to increase cellular PC and stimulate PC and cholesterol efflux mediated by ABCA1, a transporter crucial for high-density lipoprotein (HDL) generation.
Purpose of the Study:
- To investigate the effect of SM depletion on PC efflux mediated by ABCB4.
- To compare the function of ABCB4 and ABCA1 under conditions of SM depletion.
Main Methods:
- Utilized two distinct SM synthesis inhibitors: myriocin and (1R,3S)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide.
- Assessed lipid efflux activity of ABCB4 and ABCA1 in human embryonic kidney 293 and baby hamster kidney cell lines.
- Fractionated membrane proteins using Triton-X-100 and CHAPS detergents to analyze protein localization.
Main Results:
- Contrary to predictions, SM depletion suppressed PC efflux through ABCB4 while enhancing it through ABCA1.
- ABCB4 was predominantly found in CHAPS-insoluble, SM-rich membrane fractions.
- ABCA1 was primarily localized to CHAPS-soluble membrane fractions.
Conclusions:
- A sphingomyelin-rich membrane environment is essential for ABCB4 functionality.
- ABCB4 likely evolved to maximize its activity within the SM-rich environment of the hepatocyte canalicular membrane for PC transport.
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