Disease relevance of SLC29A4

• We hypothesize that ENT4, in addition to playing roles in cardiac serotonin transport, contributes to the regulation of extracellular adenosine concentrations, in particular under the acidotic conditions associated with ischemia [1].

High impact information on SLC29A4

• Five of the alanine mutants retained PMAT activity, and four were non-functional due to impaired targeting to the plasma membrane [2].
• Molecular Determinants of Substrate Selectivity of a Novel Organic Cation Transporter (PMAT) in the SLC29 Family [2].
• Northern blot analysis showed that PMAT is predominantly expressed in the human brain and widely distributed in the central nervous system [3].
• PMAT-mediated monoamine transport does not require Na(+) or Cl(-) but appears to be sensitive to changes in membrane potential [3].
• When expressed in Madin-Darby canine kidney cells and Xenopus laevis oocytes, PMAT efficiently transports serotonin (K(m) = 114 mum), dopamine (K(m) = 329 mum), and the neurotoxin 1-methyl-4-phenylpyridinium (K(m) = 33 mum) [3].

Biological context of SLC29A4

• Accordingly, we have developed a motif analysis tool for phylogenomics (Phylomat, http://alg.ncsa.uiuc.edu/pmat) that scans predicted proteome sets for proteins containing highly conserved amino acid motifs or domains for in silico analysis of the evolutionary history of these motifs/domains [4].

Anatomical context of SLC29A4

• We report here that a second member of this family, ENT4, is also abundant in the heart, in particular in the plasma membranes of ventricular myocytes and vascular endothelial cells but, unlike ENT1, is virtually absent from the sinoatrial and atrioventricular nodes [1].

Associations of SLC29A4 with chemical compounds

• However, alanine substitution at Glu(206) in TM5 abolished PMAT activity without affecting cell surface expression [2].
• 4. In contrast, serotonin transport by ENT4 was relatively insensitive to pH [1].
• ENT4-mediated nucleoside transport was adenosine selective, sodium independent and only weakly inhibited by the classical inhibitors of equilibrative nucleoside transport, dipyridamole, dilazep, and nitrobenzylthioinosine [1].
• Synthesis and some first-row transition-metal complexes of the 1,2,4-triazole-based Bis(terdentate) ligands TsPMAT and PMAT [5].

Other interactions of SLC29A4

• The ENT3 and ENT4 isoforms have more recently also been shown to be genuine nucleoside transporters [6].
• Here we report the cloning and characterization of a new human plasma membrane monoamine transporter, PMAT [3].

References