Chu Hui-Chun, Tseng Wei-Lien, Lee Hsing-Ying, Cheng Ju-Chien, Chang Shy-Shin, Yung Benjamin Yat-Ming, Tseng Ching-Ping
Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan, 333, Taiwan, Republic of China.
Cell Biol Int. 2014 Nov;38(11):1252-9. doi: 10.1002/cbin.10316. Epub 2014 Jun 6.
Iron uptake by the transferrin (Tf)-transferrin receptor (TfR) complex is critical for erythroid differentiation. The mechanisms of TfR trafficking have been examined, but the adaptor proteins involved in this process are not fully elucidated. We have investigated the role of the adaptor protein, Disabled-2 (Dab2), in erythroid differentiation and Tf uptake in the cells of hematopoietic lineage. Dab2 was upregulated in a time-dependent manner during erythroid differentiation of mouse embryonic stem cells and human K562 erythroleukemic cells. Attenuating Dab2 expression in K562 cells diminished TfR internalization and increased surface levels of TfR concomitantly with a decrease in Tf uptake and erythroid differentiation. Dab2 regulated Tf uptake of the suspended, but not adherent, cultures of K562 cells. In contrast, Dab2 is not involved in TfR trafficking in the HeLa cells with epithelial origin. These differential effects are Dab2-specific because attenuating the expression of adaptor protein 2 μ subunit inhibited the uptake of Tf regardless of culture condition. We offer novel insight of Dab2 function in iron uptake and TfR internalization for the suspended culture of hematopoietic lineage cells.
转铁蛋白（Tf）-转铁蛋白受体（TfR）复合物对铁的摄取对于红系分化至关重要。人们已经研究了TfR的运输机制，但参与这一过程的衔接蛋白尚未完全阐明。我们研究了衔接蛋白Disabled-2（Dab2）在造血谱系细胞的红系分化和Tf摄取中的作用。在小鼠胚胎干细胞和人K562红白血病细胞的红系分化过程中，Dab2以时间依赖性方式上调。在K562细胞中减弱Dab2表达会减少TfR内化，并增加TfR的表面水平，同时Tf摄取和红系分化减少。Dab2调节悬浮培养而非贴壁培养的K562细胞的Tf摄取。相反，Dab2不参与上皮来源的HeLa细胞中的TfR运输。这些差异效应具有Dab2特异性，因为减弱衔接蛋白2μ亚基的表达会抑制Tf的摄取，而与培养条件无关。我们为造血谱系细胞的悬浮培养中铁摄取和TfR内化过程中Dab2的功能提供了新的见解。
