Amino acid transporters play important roles in different human diseases. An inherited mutation of amino acid transporter B0AT1 (SLC6A19) in humans leads to poor absorption of amino acids from the gut, or poor retention of amino acids by the kidneys, leading to serious symptomatic diseases such as Hartnup disorder and iminoglycinuria (Seow et al 2004). Here we show that the B0AT1 amino acid transporter protein is expressed in mouse preimplantation embryos and the positive action of L-proline on early embryo development may rely on uptake of L-proline into the embryo by this transporter. Proline is present in mouse oviductal fluid in vivo (Guerin et al., 1995) and is accumulated in mouse embryos when added to culture media in vitro (Day Lab, unpublished). Some of the L-proline accumulation in zygotes can be attributed to expression of the transporter SIT1, which actively transports L-proline into the embryo after fertilisation until the 2-cell stage (Anas et al., 2008). L-proline uptake also involves at least one other unknown transporter, that is betaine resistant (Anas et al., 2008).
Here we found that uptake of radiolabelled L-proline by 8-cell stage embryos was reduced by the addition of excess unlabelled L-proline, L-leucine and L-glycine but not betaine, suggesting that L-proline, L-leucine and L-gylcine are transported into the embryo by the same transporter at this stage. In 8-cell stage embryos from SLC6A19-/- mice, radiolabelled L-proline uptake was decreased, compared to embryos from wild-type mice, and not significantly reduced by addition of excess unlabelled L-leucine and L-glycine, suggesting that the B0AT1 transporter may be partly responsible for L-proline uptake in the 8-cell stage embryo. Further analysis of other embryo stages will determine the role of B0AT1 in L-proline uptake and whether uptake by this transporter is required for the positive effect of L-proline on early embryo development.
- Anas, M-K. I. Lee, M.B. Zhou, C. Hammer, M.A Slow, S. Karmouch, J. X. Liu, J. Bröer, S. Lever, M. Baltz, J.M. SIT1 is a betaine/proline transporter that is activated in mouse eggs after fertilization and functions until the 2-cell stage. Development. 2008. 135: 4123-4130
- Guérin, P. Gallois, E. Croteau, S. Techniques de récolte et aminogrammes des liquids tubaire et folliculaire chez les femelles domestiques. Revue Méd. Vét. 1995. 146: 805-814.
- Seow H.F, Bröer S, Bröer A, Bailey C.G, Potter S.J, Cavanaugh J.A, Rasko J.E. Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19.Nature Genetics. 2004. 36:9:1003-1007