Bouthelier Antonio, Fernández-Arroyo Lucía, Mesa-Ciller Claudia, Cibrian Danay, Martín-Cófreces Noa Beatriz, Castillo-González Raquel, Calero Macarena, Herráez-Aguilar Diego, Guajardo-Grence Andrea, Pacheco Ana María, Marcos-Jiménez Ana, Quiroga Borja, Morado Marta, Monroy Francisco, Muñoz-Calleja Cecilia, Sánchez-Madrid Francisco, Urrutia Andrés A, Aragonés Julián
Research Unit, Hospital of Santa Cristina, Research Institute Princesa (IP), Autonomous University of Madrid, 28009 Madrid, Spain.
Immunology Department, Hospital de la Princesa, Instituto Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
iScience. 2022 Dec 5;26(1):105739. doi: 10.1016/j.isci.2022.105739. eCollection 2023 Jan 20.
Inhibition of the heterodimeric amino acid carrier SLC7A5/SLC3A2 (LAT1/CD98) has been widely studied in tumor biology but its role in physiological conditions remains largely unknown. Here we show that the SLC7A5/SLC3A2 heterodimer is constitutively present at different stages of erythroid differentiation but absent in mature erythrocytes. Administration of erythropoietin (EPO) further induces SLC7A5/SLC3A2 expression in circulating reticulocytes, as it also occurs in anemic conditions. Although gene inactivation in the erythrocyte lineage does not compromise the total number of circulating red blood cells (RBCs), their size and hemoglobin content are significantly reduced accompanied by a diminished erythroblast mTORC1 activity. Furthermore circulating -deficient reticulocytes are characterized by lower transferrin receptor (CD71) expression as well as mitochondrial activity, suggesting a premature transition to mature RBCs. These data reveal that SLC7A5/SLC3A2 ensures adequate maturation of reticulocytes as well as the proper size and hemoglobin content of circulating RBCs.
异二聚体氨基酸载体SLC7A5/SLC3A2（LAT1/CD98）的抑制作用在肿瘤生物学中已得到广泛研究，但其在生理条件下的作用仍 largely未知。在这里，我们表明SLC7A5/SLC3A2异二聚体在红细胞分化的不同阶段持续存在，但在成熟红细胞中不存在。促红细胞生成素（EPO）的给药进一步诱导循环网织红细胞中SLC7A5/SLC3A2的表达，贫血情况下也会出现这种情况。尽管红细胞谱系中的基因失活不会影响循环红细胞（RBC）的总数，但其大小和血红蛋白含量会显著降低，同时成红细胞mTORC1活性也会降低。此外，循环中缺乏该基因的网织红细胞的特征是转铁蛋白受体（CD71）表达以及线粒体活性较低，这表明它们过早地转变为成熟红细胞。这些数据表明，SLC7A5/SLC3A2可确保网织红细胞充分成熟以及循环红细胞的大小和血红蛋白含量正常。
