Gruper Yaron, Bar Jacob, Bacharach Eran, Ehrlich Rachel
Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
J Cell Physiol. 2005 Sep;204(3):901-12. doi: 10.1002/jcp.20349.
Iron uptake and storage are tightly regulated to guarantee sufficient iron for essential cellular processes and to prevent the production of damaging free radicals. The placenta is the entry site for iron, which is delivered to the developing embryo. Iron is taken up by syncytiotrophoblast cells and is transported unidirectionally from mother to fetus against a concentration gradient. Several iron transporters and regulators were recently characterized, including DMT1 and ferroportin/Ireg1 that transport iron through membranes, and HFE that regulates TfR-mediated iron uptake. In this study we demonstrate that in a differentiated choriocarcinoma cell line BeWo, HFE, and TfR are localized mainly in recycling endosomes and a small percentage of these complexes is observed in late endosomes with DMT1 while in trophoblast cells, the level of TfR is significantly lower and it is detected with HFE and DMT1 mainly in late endosomes. Most interestingly, TfR and HFE, as well as TfR and DMT1 interact in placental trophoblast cells. Based on previous and these data we suggest that the level of intracellular iron may regulate both TfR expression (on the post-transcriptional and the post-translational levels) and TfR trafficking/transcytosis in polarized cells.
铁的摄取和储存受到严格调控，以确保为基本细胞过程提供足够的铁，并防止产生具有损害性的自由基。胎盘是铁进入的部位，铁由此输送到发育中的胚胎。铁被合体滋养层细胞摄取，并逆浓度梯度从母体单向转运至胎儿。最近鉴定了几种铁转运蛋白和调节因子，包括通过细胞膜转运铁的二价金属离子转运体1（DMT1）和铁转运蛋白/铁调节蛋白1（ferroportin/Ireg1），以及调节转铁蛋白受体（TfR）介导的铁摄取的遗传性血色素沉着症蛋白（HFE）。在本研究中，我们证明，在分化的绒毛膜癌细胞系BeWo中，HFE和TfR主要定位于循环内体，并且在晚期内体中观察到这些复合物的一小部分与DMT1在一起，而在滋养层细胞中，TfR的水平显著较低，并且主要在晚期内体中与HFE和DMT1一起被检测到。最有趣的是，TfR与HFE以及TfR与DMT1在胎盘滋养层细胞中相互作用。基于先前的和这些数据，我们认为细胞内铁水平可能在转录后和翻译后水平上调节TfR表达以及TfR在极化细胞中的运输/转胞吞作用。
