Overview
- Peptide (C)EQETKLDLISKGEEPR, corresponding to amino acid residues 245-260 of human ENT1 (Accession Q99808). 3rd intracellular loop.
- Rat kidnay and brain lysates (1:200).
Western blot analysis of rat kidney lysates (lanes 1 and 3) and rat brain membranes (lanes 2 and 4):1,2. Anti-ENT1 (SLC29A1) Antibody (#ANT-051), (1:200).
3,4. Anti-ENT1 (SLC29A1) Antibody, preincubated with ENT1/SLC29A1 Blocking Peptide (#BLP-NT051).
- Rat dorsal root ganglion sections (frozen) (1:100).
Nucleosides play other important roles beyond their nucleic acid synthesis building block role. For example, they are involved in energy metabolism; they serve as ligands of purinergic receptors and act as influential signaling molecules1. Being hydrophilic, nucleosides cannot simply diffuse across the plasma membrane in order to exert their various functions, but rather need to be physically transported via nucleoside transporters1,2.
Two different transporter families are responsible for transporting nucleosides across the plasma membrane: The Concentrative Nucleoside Transporter proteins (CNT, SLC28 family), which consist of three members, CNT1-3, and act as Na+-dependent symporters1,3, and the Equilibrative Nucleoside Transporter proteins ENT1-4 (ENT, SLC29 family), which mediate Na+-independent facilitated diffusion. ENTs act as bidirectional carriers, responsible for the influx and efflux of substrates1.
Structurally, ENT transporters have eleven transmembrane domains with an intracellular N-terminal and an extracellular C-terminal1.
The best characterized ENT transporters are ENT1 and ENT2, which, although display a broader range of substrate selectivity, have lower affinities for nucleosides compared to concentrative transporters. They are ubiquitously expressed. For example, ENT1 is expressed in erythrocytes, vascular endothelium, the placenta, brain, heart, liver and colon1,4. ENT2 displays more or less the same expression pattern but in addition, is strongly expressed in skeletal muscle1,5. ENT3 is a lysosomal pH-dependent transporter capable of transporting adenine, and ENT4 also transports adenine at acidic pH. They are also broadly expressed with ENT3 displaying high expression in the placenta and ENT4 in the heart6,7.
As mentioned above, nucleosides have a variety of cellular/physiological functions suggesting that transporters responsible for their trafficking may also have functional attributes. Indeed, ENT1 plays a role in proliferation and therefore is responsible for the constitutive trafficking of nucleosides1.
There is no evidence that nucleoside transporters are directly involved in pathophysiologies, but they are clinically significant. For example, nucleoside transporters are responsible for the cellular uptake of a number of nucleoside-derived anticancer drugs1.
