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2015 ; 56
(3
): 644-652
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ABCB4 exports phosphatidylcholine in a sphingomyelin-dependent manner
#MMPMID25601960
Zhao Y
; Ishigami M
; Nagao K
; Hanada K
; Kono N
; Arai H
; Matsuo M
; Kioka N
; Ueda K
J Lipid Res
2015[Mar]; 56
(3
): 644-652
PMID25601960
show ga
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.