PMID- 24576892
OWN - NLM
STAT- MEDLINE
DCOM- 20140623
LR  - 20220317
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1841
IP  - 6
DP  - 2014 Jun
TI  - Caveolin-1 interacts with ATP binding cassette transporter G1 (ABCG1) and 
      regulates ABCG1-mediated cholesterol efflux.
PG  - 847-58
LID - S1388-1981(14)00029-8 [pii]
LID - 10.1016/j.bbalip.2014.02.002 [doi]
AB  - ATP-binding cassette transporter G1 (ABCG1) plays an important role in macrophage 
      reverse cholesterol transport in vivo by promoting cholesterol efflux onto 
      lipidated apoA-I. However, the underlying mechanism is unclear. Here, we found 
      that ABCG1 co-immunoprecipitated with caveolin-1 (CAV1) but not with flotillin-1 
      and -2. Knockdown of CAV1 expression using siRNAs significantly reduced 
      ABCG1-mediated cholesterol efflux without detectable effect on ABCA1-mediated 
      cholesterol efflux. Disruption of the putative CAV1 binding site in ABCG1, 
      through replacement of tyrosine residues at positions 487 and 489 or at positions 
      494 and 495 with alanine (Y487AY489A and Y494AY495A), impaired the interaction of 
      ABCG1 with CAV1 and significantly decreased ABCG1-mediated cholesterol efflux. 
      The substitution of Tyr494 and Tyr495 with Phe or Trp that resulted in an intact 
      CAV1 binding site had no effect. Furthermore, Y494AY495A affected trafficking of 
      ABCG1 to the cell surface. The mutant protein is mainly located intracellularly. 
      Finally, we found that CAV1 co-immunoprecipitated with ABCG1 and regulated 
      cholesterol efflux to reconstituted HDL in THP-1-derived macrophages upon the 
      liver X receptor agonist treatment. These findings indicate that CAV1 interacts 
      with ABCG1 and regulates ABCG1-mediated cholesterol efflux.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Gu, Hong-Mei
AU  - Gu HM
AD  - Departments of Pediatrics and Biochemistry, The Group on the Molecular and Cell 
      Biology of Lipids, University of Alberta, Edmonton, AB T6G 2S2, Canada.
FAU - Wang, Fa-Qi
AU  - Wang FQ
AD  - Departments of Pediatrics and Biochemistry, The Group on the Molecular and Cell 
      Biology of Lipids, University of Alberta, Edmonton, AB T6G 2S2, Canada.
FAU - Zhang, Da-Wei
AU  - Zhang DW
AD  - Departments of Pediatrics and Biochemistry, The Group on the Molecular and Cell 
      Biology of Lipids, University of Alberta, Edmonton, AB T6G 2S2, Canada. 
      Electronic address: dzhang@ualberta.ca.
LA  - eng
GR  - MOP93794/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140224
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (ABCG1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Caveolin 1)
RN  - 0 (Liver X Receptors)
RN  - 0 (Membrane Proteins)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (flotillins)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/genetics/*metabolism
MH  - Binding Sites
MH  - Biological Transport/genetics
MH  - Caveolin 1/antagonists & inhibitors/genetics/*metabolism
MH  - Cholesterol/genetics/*metabolism
MH  - Humans
MH  - Liver X Receptors
MH  - Membrane Proteins/metabolism
MH  - Orphan Nuclear Receptors/antagonists & inhibitors
MH  - Protein Binding/*genetics
MH  - RNA, Small Interfering
OTO - NOTNLM
OT  - ABC transporter
OT  - Caveolin
OT  - Cholesterol efflux
EDAT- 2014/03/01 06:00
MHDA- 2014/06/24 06:00
CRDT- 2014/03/01 06:00
PHST- 2013/07/04 00:00 [received]
PHST- 2014/02/06 00:00 [revised]
PHST- 2014/02/12 00:00 [accepted]
PHST- 2014/03/01 06:00 [entrez]
PHST- 2014/03/01 06:00 [pubmed]
PHST- 2014/06/24 06:00 [medline]
AID - S1388-1981(14)00029-8 [pii]
AID - 10.1016/j.bbalip.2014.02.002 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2014 Jun;1841(6):847-58. doi: 10.1016/j.bbalip.2014.02.002. 
      Epub 2014 Feb 24.