Miyauchi S, Srinivas S R, Fei Y-J, Gopal E, Umapathy N S, Wang H, Conway S J, Ganapathy V, Prasad P D
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA.
Placenta. 2006 Jun-Jul;27(6-7):550-9. doi: 10.1016/j.placenta.2005.05.004. Epub 2005 Aug 29.
NaS2 is a Na+-coupled transporter for sulfate that belongs to the SLC13 gene family. This transporter was originally cloned from high endothelial venule endothelial cells, but nothing is known about the functional characteristics of this transporter except that it transports sulfate in a Na+-coupled manner. Northern blot analysis indicates that NaS2 is expressed most robustly in placenta. In the present study, we cloned NaS2 from rat placenta and characterized its transport function in detail using the Xenopus laevis oocyte expression system. Rat NaS2 consists of 629 amino acids and is highly similar to human NaS2. In situ hybridization studies with mouse placental sections show that NaS2 transcripts are expressed primarily in trophoblasts of the labyrinth zone. The expression of the transporter is confirmed in primary cultures of trophoblasts isolated from human placenta. When expressed in X. laevis oocytes, rat NaS2 mediates Na+-coupled transport of sulfate. The transport of sulfate is inhibited by oxyanions of selenium, chromium, arsenic, molybdenum, and phosphorous, suggesting that the transporter may mediate the transport of these oxyanions in addition to sulfate. The Kt for sulfate is 153+/-30 microM and the Na+:sulfate stoichiometry is 3:1. The transport process is electrogenic as evidenced from the inhibition of the uptake process by K+-induced depolarization. We conclude that NaS2 is a placenta-specific Na+-coupled, electrogenic, transporter for sulfate expressed in trophoblasts and that it is also responsible for the transport of oxyanions of the micronutrients selenium and chromium.
NaS2是一种与钠离子偶联的硫酸盐转运体,属于SLC13基因家族。该转运体最初是从高内皮微静脉内皮细胞中克隆出来的,但除了它以钠离子偶联的方式转运硫酸盐外,对其功能特性一无所知。Northern印迹分析表明,NaS2在胎盘中表达最为丰富。在本研究中,我们从大鼠胎盘中克隆了NaS2,并使用非洲爪蟾卵母细胞表达系统详细表征了其转运功能。大鼠NaS2由629个氨基酸组成,与人类NaS2高度相似。对小鼠胎盘切片进行的原位杂交研究表明,NaS2转录本主要在迷路区的滋养层细胞中表达。在从人胎盘中分离出的滋养层细胞原代培养物中证实了该转运体的表达。当在非洲爪蟾卵母细胞中表达时,大鼠NaS2介导硫酸盐的钠离子偶联转运。硫酸盐的转运受到硒、铬、砷、钼和磷的含氧阴离子的抑制,这表明该转运体除了转运硫酸盐外,还可能介导这些含氧阴离子的转运。硫酸盐的Kt为153±30微摩尔,钠离子与硫酸盐的化学计量比为3:1。钾离子诱导的去极化抑制摄取过程证明,转运过程是生电性的。我们得出结论,NaS2是一种胎盘特异性的、与钠离子偶联的、生电性的硫酸盐转运体,在滋养层细胞中表达,并且它还负责微量营养素硒和铬的含氧阴离子的转运。