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Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation

Antonio Bouthelier1, Lucía Fernández-Arroyo1, Claudia Mesa-Ciller1

  • 1Research Unit, Hospital of Santa Cristina, Research Institute Princesa (IP), Autonomous University of Madrid, 28009 Madrid, Spain.

Iscience
|December 30, 2022
PubMed

Insights

The amino acid transporter SLC7A5/SLC3A2 is crucial for red blood cell (RBC) maturation. Its absence leads to smaller RBCs with less hemoglobin, indicating a vital role in normal erythropoiesis.

Area of Science:

  • Cell Biology
  • Hematology
  • Physiology

Background:

  • The role of the amino acid transporter SLC7A5/SLC3A2 (LAT1/CD98) in normal physiological conditions is largely unknown, despite extensive study in cancer.
  • This transporter is implicated in cellular growth and nutrient uptake.

Purpose of the Study:

  • To investigate the physiological role of the SLC7A5/SLC3A2 heterodimer during erythroid differentiation and red blood cell maturation.
  • To determine the impact of SLC7A5/SLC3A2 deficiency on red blood cell parameters.

Main Methods:

  • Analysis of SLC7A5/SLC3A2 expression during erythroid differentiation stages.
  • Gene inactivation of Slc7a5 in the erythrocyte lineage using mouse models.
  • Assessment of red blood cell parameters, including size, hemoglobin content, transferrin receptor (CD71) expression, and mitochondrial activity.

Main Results:

  • SLC7A5/SLC3A2 is present during erythroid differentiation but absent in mature erythrocytes.
  • Erythropoietin (EPO) and anemia induce SLC7A5/SLC3A2 expression in reticulocytes.
  • Slc7a5 gene inactivation resulted in smaller RBCs with reduced hemoglobin content and diminished mTORC1 activity.
  • Slc7a5-deficient reticulocytes showed decreased CD71 expression and mitochondrial activity, suggesting premature maturation.

Conclusions:

  • The SLC7A5/SLC3A2 heterodimer is essential for proper reticulocyte maturation.
  • This transporter plays a critical role in ensuring adequate size and hemoglobin content of circulating red blood cells.
  • These findings highlight a novel physiological function of SLC7A5/SLC3A2 in hematopoiesis.
Keywords:
Cell biologyMolecular physiology

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