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The equilibrative nucleoside transporter family, SLC29
Stephen A Baldwin1, Paul R Beal, Sylvia Y M Yao
1School of Biochemistry and Molecular Biology, University of Leeds, LS2 9JT, Leeds, UK. s.a.baldwin@leeds.ac.uk
Pflugers Archiv : European Journal of Physiology
|July 3, 2003
Summary
The human SLC29 family, or equilibrative nucleoside transporters (ENTs), are crucial for nucleoside and nucleobase uptake. These transporters also influence physiological processes by regulating adenosine levels.
Area of Science:
- Molecular biology
- Cell biology
- Biochemistry
Background:
- The human SLC29 family comprises four members, known as equilibrative nucleoside transporters (ENTs).
- These transporters are distantly related to CLN3, a lysosomal membrane protein implicated in neuronal ceroid lipofuscinosis.
- A topology of 11 transmembrane helices with a cytoplasmic N-terminus and extracellular C-terminus has been confirmed for hENT1.
Purpose of the Study:
- To elucidate the structure and function of the human SLC29 family of nucleoside transporters.
- To understand the substrate specificities and tissue distribution of ENT isoforms.
- To explore the role of ENTs in physiological processes and drug uptake.
Main Methods:
- Experimental confirmation of hENT1 topology.
- Characterization of substrate specificities for hENT1, hENT2, ENT3, and ENT4.
- Analysis of tissue distribution and cellular localization of ENT isoforms.
Main Results:
- hENT1 and hENT2 exhibit broad substrate specificities for purine and pyrimidine nucleosides; hENT2 also transports nucleobases.
- ENT3 and ENT4 are confirmed nucleoside transporters.
- All four isoforms are widely distributed in mammalian tissues, with ENT2 abundant in skeletal muscle.
- ENT1 and ENT2 are localized to the basolateral membrane in polarized cells, potentially aiding transepithelial transport with SLC28 transporters.
Conclusions:
- The SLC29 family of equilibrative nucleoside transporters plays vital roles in nucleoside and nucleobase uptake for nucleotide synthesis.
- These transporters are essential for the cellular uptake of nucleoside analogues used in cancer and antiviral therapies.
- By modulating extracellular adenosine concentrations, ENTs significantly influence diverse physiological processes, including cardiovascular activity and neurotransmission.