TY - JOUR
T1 - ABCB4 exports phosphatidylcholine in a sphingomyel-independent manner
AU - Zhao, Yu
AU - Ishigami, Masato
AU - Nagao, Kohjiro
AU - Hanada, Kentaro
AU - Kono, Nozomu
AU - Arai, Hiroyuki
AU - Matsuo, Michinori
AU - Kioka, Noriyuki
AU - Ueda, Kazumitsu
N1 - Publisher Copyright:
Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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.
AB - 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.
KW - ( 1R,3S )-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide
KW - ATP binding cassette protein
KW - ATP binding cassette transporter A1
KW - Bile acid
KW - Cholesterol
KW - High density lipoprotein
KW - Myriosin
UR - http://www.scopus.com/inward/record.url?scp=84925340682&partnerID=8YFLogxK
U2 - 10.1194/jlr.M056622
DO - 10.1194/jlr.M056622
M3 - 記事
C2 - 25601960
AN - SCOPUS:84925340682
SN - 0022-2275
VL - 56
SP - 644
EP - 652
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 3
ER -