Transferrin receptor 1 is required for enucleation of mouse erythroblasts during terminal differentiation
Transferrin receptor 1 is required for enucleation of mouse erythroblasts during terminal differentiation
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DOI：
10.1002/2211-5463.12573
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发表时间：
2019-02-01
期刊：
影响因子：
2.6
通讯作者：
Mitsuda, Noriaki
中科院分区：
文献类型：
--
作者：
Aoto, Mamoru;Iwashita, Akiho;Mitsuda, Noriaki
去核是在哺乳动物红细胞生成后期，细胞核从成红细胞中挤出的过程。然而，参与这一过程的具体信号通路仍不清楚。为了更好地了解成红细胞去核的机制，我们研究了成红细胞去核，使用苯肼诱导贫血的成年小鼠的脾脏和小鼠胎肝。我们的研究结果表明，铁结合转铁蛋白（holo-Tf）和小分子铁转运蛋白扁柏酚与铁离子（扁柏酚加铁）促进血红蛋白的合成和小鼠脾衍生的成红细胞去核。虽然抗转铁蛋白受体1（TfR 1）的单克隆抗体抑制去核和血红蛋白的合成促进全转铁蛋白，它只抑制去核，但不血红蛋白的合成，促进扁柏酚加铁。此外，针对小鼠TfR 1的siRNA被发现抑制小鼠胎肝衍生的成红细胞的去核，并且内吞作用抑制剂MitMAB抑制由两种类型的刺激促进的去核、血红蛋白合成和TfR 1的内化。总的来说，我们的研究结果表明，TfR 1，铁离子，和内吞作用在小鼠成红细胞去核中发挥重要作用。
Enucleation is the process whereby the nucleus is extruded from the erythroblast during late stage mammalian erythropoiesis. However, the specific signaling pathways involved in this process remain unclear. To better understand the mechanisms underlying erythroblast enucleation, we investigated erythroblast enucleation using both the spleens of adult mice with phenylhydrazine-induced anemia and mouse fetal livers. Our results indicated that both iron-bound transferrin (holo-Tf) and the small-molecule iron transporter hinokitiol with iron ions (hinokitiol plus iron) promote hemoglobin synthesis and the enucleation of mouse spleen-derived erythroblasts. Although an antitransferrin receptor 1 (TfR1) monoclonal antibody inhibited both enucleation and hemoglobin synthesis promoted by holo-Tf, it inhibited only enucleation, but not hemoglobin synthesis, promoted by hinokitiol plus iron. Furthermore, siRNA against mouse TfR1 were found to suppress the enucleation of mouse fetal liver-derived erythroblasts, and the endocytosis inhibitor MitMAB inhibited enucleation, hemoglobin synthesis, and the internalization of TfR1 promoted by both types of stimuli. Collectively, our results suggest that TfR1, iron ions, and endocytosis play important roles in mouse erythroblast enucleation.