Localization of the nuclear receptor CAR at the cell membrane of mouse liver.
The nuclear receptor constitutive active/androstane receptor CAR is a drug-sensing transcription factor. Upon activation by various drugs such as phenobarbital (PB), CAR translocates from the cytoplasm into the nucleus to regulate the genes that encode enzymes and proteins involved in hepatic metabolism. Here, we have shown the presence of CAR at the cell membrane of mouse livers, using Car+/+ and Car-/- mice. Levels of the cell membrane CAR increased after PB treatment. The CAR exists as a large approximately 160 kDa complex. Thus, CAR undergoes PB-induced translocation to the cell membrane, indicating that CAR may exert a non-genomic action.
Koike
Chika
C
Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Moore
Rick
R
Negishi
Masahiko
M
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008110:Liver Extracts / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008970:Molecular Weight; D010634:Phenobarbital / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D013347:Subcellular Fractions / Q000737:chemistry; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D008110:Liver Extracts; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D010634:Phenobarbital