The SNAT4 isoform of the system A amino acid transporter is expressed in human placenta

The system A amino acid transporter is encoded by three members of the Slc38 gene family giving rise to three subtypes: SNAT1, SNAT2, and SNAT4. SNAT2 is expressed ubiquitously in mammalian tissues, SNAT1 is predominantly expressed in heart, brain, and placenta while SNAT4 is reported to be expressed uniquely by the liver. In the placenta, system A has an essential role in the supply of neutral amino acids needed for fetal growth. Here, we examined expression and localisation of SNAT1, 2 and 4 in human placenta over gestation. Real-time quantitative PCR was used to examine steady state levels of system A subtype mRNA in early (6-10 weeks) and late (10-13 weeks) first trimester and full term (38-40 weeks) placentas. We detected mRNA for all three isoforms from early gestation onwards. There were no differences in SNAT1 and 2 mRNA expression with gestation. However, SNAT4 mRNA expression was significantly higher in early first trimester compared to term (p<0.01). We next investigated SNAT4 protein expression in human placenta. In contrast to the observation for gene expression, Western blotting revealed that SNAT4 protein expression was significantly higher at term compared to first trimester (p<0.05). Immunohistochemistry and Western blotting showed that SNAT4 is localised to the microvillous and basal plasma membranes of the syncytiotrophoblast, suggesting a role for this isoform of system A in amino acid transport across the placenta. This study therefore provides the first evidence of SNAT4 mRNA and protein expression in human placenta at both first trimester and term. 3 Introduction: System A is a ubiquitous Na +-dependent transporter that actively transports small,