The equilibrative nucleoside transporter family, SLC29

Abstract

The human SLC29 family of proteins contains four members, designated equilibrative nucleoside transporters (ENTs) because of the properties of the first-characterised family member, hENT1. They belong to the widely-distributed eukaryotic ENT family of equilibrative and concentrative nucleoside/nucleobase transporters and are distantly related to a lysosomal membrane protein, CLN3, mutations in which cause neuronal ceroid lipofuscinosis. A predicted topology of 11 transmembrane helices with a cytoplasmic N-terminus and an extracellular C-terminus has been experimentally confirmed for hENT1. The best-characterised members of the family, hENT1 and hENT2, possess similar broad substrate specificities for purine and pyrimidine nucleosides, but hENT2 in addition efficiently transports nucleobases. The ENT3 and ENT4 isoforms have more recently also been shown to be genuine nucleoside transporters. All four isoforms are widely distributed in mammalian tissues, although their relative abundance varies: ENT2 is particularly abundant in skeletal muscle. In polarised cells ENT1 and ENT2 are found in the basolateral membrane and, in tandem with concentrative transporters of the SLC28 family, may play a role in transepithelial nucleoside transport. The transporters play key roles in nucleoside and nucleobase uptake for salvage pathways of nucleotide synthesis, and are also responsible for the cellular uptake of nucleoside analogues used in the treatment of cancers and viral diseases. In addition, by regulating the concentration of adenosine available to cell surface receptors, they influence many physiological processes ranging from cardiovascular activity to neurotransmission.

Circadian rhythms and sleep—the metabolic connection

“…Extracellular ATP is rapidly degraded by ectonucleotidases [85], some of which are expressed in a timedependent fashion [83]. The resulting adenosine accumulates in the extracellular space and is taken up by astrocytes via equilibrative nucleoside transporters [4]. Inside the cell, adenosine is phosphorylated by adenosine kinase (ADK) to 5′-AMP.…”

Equilibrative nucleoside transporters—A review

“…Two classes of nucleoside transporters mediate physiologic nucleoside transport across cellular membranes: equilibrative nucleoside transporters (ENTs, SLC29 family) and concentrative nucleoside transporters (CNTs, SLC28 family) (4, 5). The CNT and ENT families are structurally unrelated nucleoside transporters with overlapping substrate specificities.…”

Regulation of hepatic glucose production and AMPK by AICAR but not by metformin depends on drug uptake through the equilibrative nucleoside transporter 1 (ENT1)

“…Importantly, it has been reported previously that 8CPT‐modified cAMP analogues inhibit nucleoside transporters,23 which are divided into two different families: constitutive nucleoside transporters (CNT) (SLC28), of which there are three members (CNT1‐3) or equilibrative nucleoside transporters (ENT) (SLC29), of which there are four members (ENT1‐4) 29. These nucleoside transporters are responsible for transporting nucleosides such as adenosine and uridine into the cell.…”