RT Journal Article T1 Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation A1 Bouthelier, Antonio A1 Fernández- Arroyo, Lucía A1 Mesa Ciller, Claudia A1 Cibrian, Danay A1 Martín Cofreces, Noa Beatriz A1 Castillo González, Raquel A1 Calero Calero, Macarena A1 Herráez Aguilar, Diego A1 Guajardo Grence, Andrea A1 Pacheco, Ana María A1 Marcos Jiménez, Ana A1 Quiroga, Borja A1 Morado, Marta A1 Morado, Marta A1 Monroy Muñoz, Francisco A1 Muñoz Calleja, Cecilia A1 Sánchez Madrid, Francisco A1 Urrutia, Andrés A A1 Aragonés, Julián AB 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 Slc7a5 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 Slc7a5-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. PB Elsevier SN 2589-0042 YR 2023 FD 2023 LK https://hdl.handle.net/20.500.14352/93189 UL https://hdl.handle.net/20.500.14352/93189 LA eng NO Bouthelier, A.; Fernández-Arroyo, L.; Mesa-Ciller, C.; Cibrian, D.; Martín-Cófreces, N. B.; Castillo-González, R.; Calero, M.; Herráez-Aguilar, D.; Guajardo-Grence, A.; Pacheco, A. M.; Marcos-Jiménez, A.; Quiroga, B.; Morado, M.; Monroy, F.; Muñoz-Calleja, C.; Sánchez-Madrid, F.; Urrutia, A. A.; Aragonés, J. Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation. iScience 2023, 26, 105739 DOI:10.1016/j.isci.2022.105739. NO Ministerio de Ciencia, Innovación y Universidades (España) NO Ministerio de Economía y Competitividad (España) DS Docta Complutense RD 17 abr 2025