PUBLICATION
The flounder organic anion transporter fOat has sequence, function, and substrate specificity similarity to both mammalian Oat1 and Oat3
- Authors
- Aslamkhan, A.G., Thompson, D.M., Perry, J.L., Bleasby, K., Wolff, N.A., Barros, S., Miller, D.S., and Pritchard, J.B.
- ID
- ZDB-PUB-060724-30
- Date
- 2006
- Source
- American journal of physiology. Regulatory, integrative and comparative physiology 291(6): R1773-R1780 (Journal)
- Registered Authors
- Keywords
- OAT1, OAT3, renal, isolated tubules
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Evolution, Molecular
- Flounder/genetics*
- Flounder/metabolism*
- Humans
- Molecular Sequence Data
- Organic Anion Transport Protein 1/chemistry
- Organic Anion Transport Protein 1/genetics
- Organic Anion Transport Protein 1/metabolism
- Organic Anion Transporters, Sodium-Independent/chemistry
- Organic Anion Transporters, Sodium-Independent/genetics*
- Organic Anion Transporters, Sodium-Independent/metabolism*
- Sequence Homology, Amino Acid
- Species Specificity
- Substrate Specificity
- PubMed
- 16857889 Full text @ Am. J. Physiol. Regul. Integr. Comp. Physiol.
Citation
Aslamkhan, A.G., Thompson, D.M., Perry, J.L., Bleasby, K., Wolff, N.A., Barros, S., Miller, D.S., and Pritchard, J.B. (2006) The flounder organic anion transporter fOat has sequence, function, and substrate specificity similarity to both mammalian Oat1 and Oat3. American journal of physiology. Regulatory, integrative and comparative physiology. 291(6):R1773-R1780.
Abstract
The flounder renal organic anion transporter (fOat) has substantial sequence homology to mammalian basolateral organic anion transporter orthologs (OAT1/Oat1 and OAT3/Oat3) suggesting that fOat might have functional properties of both mammalian forms. We therefore compared uptake of various substrates by rat Oat1 and Oat3 and human OAT1 and OAT3 with the fOat clone expressed in Xenopus oocytes. These data confirm that estrone sulfate is an excellent substrate for mammalian OAT3/Oat3s, but not for OAT1/Oat1s. In contrast, 2,4-dichlorophenoxyacetic acid and adefovir are better transported by mammalian OAT1/Oat1 than by the OAT3/Oat3 clones. All three substrates were well transported by fOat-expressing Xenopus oocytes. fOat Km values were comparable to those obtained for mammalian OAT/Oat1/3 clones. We also characterized the ability of these substrates to inhibit uptake of the fluorescent substrate, fluorescein, in intact teleost proximal tubules isolated from the winter flounder (Pseudopleuronectes americanus) and killifish (Fundulus hereroclitus). The rank order of the IC50s for inhibition of cellular fluorescein accumulation was similar to that for the Km values obtained in fOat expressing oocytes, suggesting fOat may be the primary teleost renal basolateral Oat. Assessment of the zebrafish (Danio rerio) genome indicated the presence of a single Oat (zfOat) with similarity to both mammalian OAT1/Oat1 and OAT3/Oat3. The puffer fish (Takifugu rubripes) also has an Oat (pfOat) similar to mammalian OAT1/Oat1 and OAT3/Oat3 members. Furthermore, phylogenetic analyses argue that the teleost Oat1/3-like genes diverged from a common ancestral gene in advance of the divergence of the mammalian OAT1/Oat1, OAT3/Oat3 and possibly Oat6 genes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping