ABCB4 exports phosphatidylcholine in a sphingomyelin-dependent manner

作者：Zhao Yu; Ishigami Masato; Nagao Kohjiro; Hanada Kentaro; Kono Nozomu; Arai Hiroyuki; Matsuo Michinori; Kioka Noriyuki; Ueda Kazumitsu^*

来源：The Journal of Lipid Research, 2015, 56(3): 644-652.

DOI：10.1194/jlr.M056622

• ATP binding cassette protein
• ATP binding cassette transporter A1
• myriosin
• cholesterol
• high density lipoprotein
• (1R,3S)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide
• bile acid

ABCB4, which is specifically expressed on the canalicular membrane of hepatocytes, exports phosphatidylcholine (PC) into bile. Because SM depletion increases cellular PC content and stimulates PC and cholesterol efflux by ABCA1, a key transporter involved in generation of HDL, we predicted that SM depletion also stimulates PC efflux through ABCB4. To test this prediction, we compared the lipid efflux activity of ABCB4 and ABCA1 under SM depletion induced by two different types of inhibitors for SM synthesis, myriocin and (1R, 3S)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide, in human embryonic kidney 293 and baby hamster kidney cells. Unexpectedly, SM depletion exerted opposite effects on ABCB4 and ABCA1, suppressing PC efflux through ABCB4 while stimulating efflux through ABCA1. Both ABCB4 and ABCA1 were recovered from Triton-X-100-soluble membranes, but ABCB4 was mainly recovered from CHAPS-insoluble SM-rich membranes, whereas ABCA1 was recovered from CHAPS-soluble membranes. These results suggest that a SM-rich membrane environment is required for ABCB4 to function. ABCB4 must have evolved to exert its maximum activity in the SM-rich membrane environment of the canalicular membrane, where it transports PC as the physiological substrate.

• 出版日期2015-3