Reduced-folate carrier (RFC) is expressed in placenta and yolk sac, as well as in cells of the developing forebrain, hindbrain, neural tube, craniofacial region, eye, limb buds and heart.
Reduced-folate carrier (RFC) is expressed in placenta and yolk sac, as well as in cells of the developing forebrain, hindbrain, neural tube, craniofacial region, eye, limb buds and heart.
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DOI：
10.1186/1471-213x-3-6
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发表时间：
2003-07-29
影响因子：
--
通讯作者：
Smith SB
中科院分区：
文献类型：
--
作者：
Maddox DM;Manlapat A;Roon P;Prasad P;Ganapathy V;Smith SB
叶酸对细胞增殖和组织再生至关重要。由于哺乳动物细胞不能从头合成叶酸，因此严格调节的细胞摄取过程已经进化为维持足够水平的细胞内四氢叶酸辅因子以支持嘌呤、嘧啶和一些氨基酸（丝氨酸、甲硫氨酸）的生物合成。还原型叶酸载体（reduced-folate carrier，RFC）是介导叶酸转运的主要蛋白质之一，但对RFC在发育过程中的表达尚缺乏了解。我们利用原位杂交和免疫定位，以确定RFC信息和蛋白质的发育分布，分别。在小鼠中，RFC转录本和蛋白质在E10.0胎盘和卵黄囊中表达。在E9.0至E11.5小鼠胚胎中，RFC被广泛检测到，强烈的信号定位于神经管、颅面区域、肢芽和心脏中的细胞群。在早期发育过程中，RFC在整个眼睛中表达，但到E12.5，RFC蛋白定位于视网膜色素上皮（RPE）。临床研究表明，在怀孕期间补充叶酸的女性患者的后代中检测到的神经管缺陷、颅面畸形、心血管缺陷和肢体畸形的数量在统计学上有所减少。然而，叶酸补充剂改善发育缺陷发生的机制尚不清楚。目前的工作表明，RFC存在于胎盘和卵黄囊，并提供了第一个证据表明，它是在神经管，颅面区，肢芽和心脏器官发生过程中表达。这些发现表明，在发育中的神经管、颅面区域、肢芽和心脏中快速分裂的细胞可能特别容易受到叶酸缺乏的影响。
Folate is essential for cellular proliferation and tissue regeneration. As mammalian cells cannot synthesize folates de novo, tightly regulated cellular uptake processes have evolved to sustain sufficient levels of intracellular tetrahydrofolate cofactors to support biosynthesis of purines, pyrimidines, and some amino acids (serine, methionine). Though reduced-folate carrier (RFC) is one of the major proteins mediating folate transport, knowledge of the developmental expression of RFC is lacking. We utilized in situ hybridization and immunolocalization to determine the developmental distribution of RFC message and protein, respectively. In the mouse, RFC transcripts and protein are expressed in the E10.0 placenta and yolk sac. In the E9.0 to E11.5 mouse embryo RFC is widely detectable, with intense signal localized to cell populations in the neural tube, craniofacial region, limb buds and heart. During early development, RFC is expressed throughout the eye, but by E12.5, RFC protein becomes localized to the retinal pigment epithelium (RPE). Clinical studies show a statistical decrease in the number of neural tube defects, craniofacial abnormalities, cardiovascular defects and limb abnormalities detected in offspring of female patients given supplementary folate during pregnancy. The mechanism, however, by which folate supplementation ameliorates the occurrence of developmental defects is unclear. The present work demonstrates that RFC is present in placenta and yolk sac and provides the first evidence that it is expressed in the neural tube, craniofacial region, limb buds and heart during organogenesis. These findings suggest that rapidly dividing cells in the developing neural tube, craniofacial region, limb buds and heart may be particularly susceptible to folate deficiency.