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Erythroid 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 different...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9792907/
https://www.ncbi.nlm.nih.gov/pubmed/36582828
http://dx.doi.org/10.1016/j.isci.2022.105739
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author 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
author_facet 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
author_sort Bouthelier, Antonio
collection PubMed
description 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.
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spelling pubmed-97929072022-12-28 Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation 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 iScience Article 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. Elsevier 2022-12-05 /pmc/articles/PMC9792907/ /pubmed/36582828 http://dx.doi.org/10.1016/j.isci.2022.105739 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
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
Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation
title Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation
title_full Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation
title_fullStr Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation
title_full_unstemmed Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation
title_short Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation
title_sort erythroid slc7a5/slc3a2 amino acid carrier controls red blood cell size and maturation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9792907/
https://www.ncbi.nlm.nih.gov/pubmed/36582828
http://dx.doi.org/10.1016/j.isci.2022.105739
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