biostudies-literatureUnknown26(1)Bouthelier AInhibition 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 <i>Slc7a5</i> 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 <i>Slc7a5</i>-deficieniScience105739https://www.ebi.ac.uk/biostudies/studies/S-EPMC9792907biostudies-literatureErythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation.PMC9792907Cibrian DMarcos-Jimenez AMonroy FPacheco AMQuiroga BBouthelier ACastillo-Gonzalez RSanchez-Madrid FAragones JMorado MUrrutia AAGuajardo-Grence ACalero MMunoz-Calleja CFernandez-Arroyo LMesa-Ciller CMartin-Cofreces NBHerraez-Aguilar DfalseErythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation.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 <i>Slc7a5</i> 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 <i>Slc7a5</i>-deficien2023-01-01T00:00:00Z2023 Jan2025-04-04T14:10:49.327Z2025-04-04T14:10:49.327ZS-EPMC97929073658282810.1016/j.isci.2022.105739