The DOI matches its Crossref record.
ABCG5 and ABCG8 Are Obligate Heterodimers for Protein Trafficking and Biliary Cholesterol Excretion
Open accessAbstract
ABCG5 (G5) and ABCG8 (G8) are ATP-binding cassette (ABC) transporters that limit intestinal absorption and promote biliary excretion of neutral sterols. Mutations in either ABCG5 or ABCG8 result in an identical clinical phenotype, suggesting that these two half-transporters function as heterodimers. Expression of both G5 and G8 is required for either protein to be transported to the plasma membrane of cultured cells. In this paper we used immunofluorescence microscopy to confirm, in vivo, that G5 is localized to the apical membranes of mouse enterocytes and hepatocytes. Other ABC half-transporters function as homodimers or as heterodimers with other subfamily members. To determine whether G5 or G8 complex with other ABCG half-transporters, we co-expressed G1, G2, and G4 with either G5 or G8 in cultured cells. G1, G2, and G4 co-immunoprecipitated with G5, and G4 co-immunoprecipitated with G8, but the putative dimers were retained in the endoplasmic reticulum (ER). Adenovirus-mediated expression of either G5 or G8 in the liver of G5G8 null mice resulted in ER retention of the expressed proteins and no increase in biliary cholesterol. In contrast, co-expression of G5 and G8 resulted in transit of the proteins out of the ER and a 10-fold increase in biliary cholesterol concentration. Finally, adenoviral expression of G2 in the presence or absence of G5 or G8 failed to promote sterol excretion into bile. These experiments indicate that G5 and G8 function as obligate heterodimers to promote sterol excretion into bile.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
Mechanisms and regulation of cholesterol homeostasis
Luo, J., Yang, H., & Song, B.-L. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0190-7 · Cited by 1,980
Pleiotropic Roles of Bile Acids in Metabolism
de Aguiar Vallim, T. Q., Tarling, E. J., & Edwards, P. A. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.013 · Cited by 1,209
Liver X receptors in lipid signalling and membrane homeostasis
Wang, B., & Tontonoz, P. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0037-x · Cited by 722
ATP-Binding Cassette Cholesterol Transporters and Cardiovascular Disease
Oram, J. F., & Vaughan, A. M. (2006) · Circulation Research · doi:10.1161/01.res.0000250171.54048.5c · Cited by 411
The TMAO-Generating Enzyme Flavin Monooxygenase 3 Is a Central Regulator of Cholesterol Balance
Warrier, M., Shih, D. M., Burrows, A. C., Ferguson, D., Gromovsky, A. D., Brown, A. L., Marshall, S., McDaniel, A., Schugar, R. C., Wang, Z., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2014.12.036 · Cited by 414
Cholesterol, the central lipid of mammalian cells
Maxfield, F. R., & van Meer, G. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2010.05.004 · Cited by 414
Niemann-Pick C1-Like 1 (NPC1L1) Protein in Intestinal and Hepatic Cholesterol Transport
Jia, L., Betters, J. L., & Yu, L. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-012110-142233 · Cited by 356
Self-citationMechanisms for cellular cholesterol transport: Defects and human disease
Ikonen, E. (2006) · Physiological Reviews · doi:10.1152/physrev.00022.2005 · Cited by 229
Expression of ABCG5 and ABCG8 Is Required for Regulation of Biliary Cholesterol Secretion
Yu, L., Gupta, S., Xu, F., Liverman, A. D. B., Moschetta, A., Mangelsdorf, D. J., Repa, J. J., Hobbs, H. H., & Cohen, J. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411080200 · Cited by 192
Self-citationThyroid hormone signaling and the liver
Ritter, M. J., Amano, I., Hollenberg, A. N., et al. (2020) · Hepatology · doi:10.1002/hep.31296 · Cited by 188
Wang, N., Yvan‐Charvet, L., Lütjohann, D., Mulder, M., Vanmierlo, T., Kim, T., & Tall, A. R. (2008) · The FASEB Journal · doi:10.1096/fj.07-9944com · Cited by 184
Suzuki, T., Ishihara, K., Migaki, H., Ishihara, K., Nagao, M., Yamaguchi-Iwai, Y., & Kambe, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506902200 · Cited by 168
Boyer, J. L. (2013) · Comprehensive Physiology · doi:10.1002/j.2040-4603.2013.tb00519.x · Cited by 124
GPR146 Deficiency Protects against Hypercholesterolemia and Atherosclerosis
Yu, H., Rimbert, A., Palmer, A. E., Toyohara, T., Xia, Y., Xia, F., Ferreira, L. M. R., Chen, Z., Chen, T., Loaiza, N., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.034 · Cited by 113
Plummer, A. M., Culbertson, A. T., & Liao, M. (2021) · Annual Review of Physiology · doi:10.1146/annurev-physiol-031620-094944 · Cited by 60
Horenstein, R. B., Mitchell, B. D., Post, W. S., Lütjohann, D., von Bergmann, K., Ryan, K. A., Terrin, M., Shuldiner, A. R., & Steinle, N. I. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.245480 · Cited by 36
Metadata
- Authors
- Graf, G. A., Yu, L., Li, W.-P., Gerard, R., Tuma, P. L., Cohen, J. C., & Hobbs, H. H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 278
- Issue
- 48
- Pages
- 48275-48282
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2156504663
- Cited by
- 475
- References
- 0
- FWCI
- 24.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
