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Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient
David J Seward1, Albert S Koh, James L Boyer
1Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York 14642, USA.
The Journal of Biological Chemistry
|April 30, 2003
Summary
Researchers discovered a novel organic solute transporter (OST) formed by co-expressing OSTalpha and OSTbeta proteins. This transporter functions across species, facilitating the transport of estrone 3-sulfate and other substances.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- Organic solute transporters are crucial for cellular function and drug disposition.
- The specific mechanisms and protein interactions involved in organic solute transport are not fully understood.
Purpose of the Study:
- To identify and characterize a novel organic solute transporter (OST) complex.
- To investigate the functional complementation and species-specific interactions of OSTalpha and OSTbeta subunits.
Main Methods:
- Cloning and sequencing of human and mouse OSTalpha and OSTbeta cDNAs.
- Expression of OST proteins in Xenopus laevis oocytes.
- Functional assays measuring [3H]estrone 3-sulfate transport and substrate specificity.
Main Results:
- Co-expression of OSTalpha and OSTbeta subunits from human, mouse, or skate generated functional estrone 3-sulfate transport.
- Individual subunits did not elicit transport, but co-expression was not required for membrane targeting.
- The transporter exhibited sodium-independent, saturable kinetics and transported various substrates including taurocholate and digoxin.
- OSTalpha and OSTbeta mRNAs were widely distributed in human tissues, notably in the testis and liver.
Conclusions:
- A heterodimeric organic solute transporter (OST) is formed by OSTalpha and OSTbeta subunits.
- This OST complex demonstrates functional conservation across mammalian and fish species.
- The transporter plays a significant role in the disposition of various organic solutes and is broadly expressed in human tissues.