The zebrafish (Danio rerio) aryl hydrocarbon receptor type 1 is a novel vertebrate receptor.

TitleThe zebrafish (Danio rerio) aryl hydrocarbon receptor type 1 is a novel vertebrate receptor.
Publication TypeJournal Article
Year of Publication2002
AuthorsAndreasen, EA, Hahn, ME, Heideman, W, Peterson, RE, Tanguay, RL
JournalMol Pharmacol
Date Published2002 Aug
KeywordsAmino Acid Sequence, Animals, Binding, Competitive, COS Cells, Dioxins, DNA, Complementary, Molecular Sequence Data, Phylogeny, Protein Structure, Tertiary, Radioligand Assay, Receptors, Aryl Hydrocarbon, RNA, Messenger, Sequence Homology, Amino Acid, Tissue Distribution, Transcriptional Activation, Zebrafish

Fish are known to have two distinct classes of aryl hydrocarbon receptors, and their roles in mediating xenobiotic toxicity remain unclear. In this study, we have identified and characterized a cDNA tentatively named zebrafish AHR1 (zfAHR1). Analysis of the deduced amino acid sequence reveals that the protein is distinct from zfAHR2 and is more closely related to the mammalian aryl hydrocarbon receptor (AHR). zfAHR1 and zfAHR2 share 40% amino acid identity overall and 58% in the N-terminal half. The zfAHR1 gene maps to linkage group 16 in a region that shares conserved synteny with human chromosome 7 containing the human AHR, suggesting that the zfAHR1 is the ortholog of the human AHR. zfAHR2 maps to a separate linkage group (LG22). Both zfAHR mRNAs are expressed in early development, but they are differentially expressed in adult tissues. zfAHR2 can dimerize with zfARNT2b and binds with specificity to dioxin-responsive elements (DREs). Under identical conditions, zfAHR1/zfARNT2b/DRE complexes are formed; however, the interactions are considerably weaker. In COS-7 cells expressing zfARNT2b and zfAHR2, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure leads to a significant induction of dioxin-responsive reporter genes. In identical experiments, TCDD exposure fails to induce the reporter gene in zfAHR1-expressing cells. Ligand-binding experiments suggested that the differential zfAHR activities are attributable to differences in TCDD binding because only zfAHR2 exhibits high-affinity binding to [(3)H]TCDD or beta-naphthoflavone. Finally, using chimeric zfAHR1/zfAHR2 constructs, the lack of TCDD-mediated transcriptional activity was localized to the ligand-binding and C-terminal domains of zfAHR1.

Alternate JournalMol. Pharmacol.
PubMed ID12130674
Grant ListR01 ES006272 / ES / NIEHS NIH HHS / United States
ES06272 / ES / NIEHS NIH HHS / United States
ES10820 / ES / NIEHS NIH HHS / United States
P30-ES09090 / ES / NIEHS NIH HHS / United States
R01 ES010820-01 / ES / NIEHS NIH HHS / United States
R01 ES010820 / ES / NIEHS NIH HHS / United States
R01 ES006272-13 / ES / NIEHS NIH HHS / United States