Function and regulation of the SNAT4 isoform of the System A amino acid transporter in human and mouse placenta. (360G-Wellcome-078814_Z_05_Z)

A wealth of data suggests that the placental System A amino acid transporter is particularly important in supplying the fetus with amino acids necessary for normal growth. Consequently, abnormal activity of this transporter may be the cause of some cases of fetal intrauterine growth restriction (IUGR). There are three different isoforms of System A (SNAT1, 2 and 4) but their relative importance to placental amino acid transport has not been established. Our preliminary data show that, i. contrar y to previous reports, SNAT4 is expressed by the placenta; ii. expression increases over gestation; iii. in a mouse model of IUGR, SNAT4 gene (Slc38a4) expression is related directly to fetal growth. However, the functional role of SNAT4 in the placenta has not been investigated. Our aim is to test the hypothesis that placental SNAT4 is functionally important in transporting specific amino acids required for normal fetal growth. We will test this hypothesis using an integrated biology approach w ith the key goals to determine: i. activity of SNAT4 in human placental trophoblast; ii. functional activity and regulation of SNAT4 in placenta over gestation iii. role of SNAT4 in amino acid supply to the fetus, using a mouse model of IUGR.