ArticleScience signaling2015
The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability.
Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 66 citations in OpenAlex.
- A short-term intervention of ingesting iron along with methionine and threonine leads to a higher hemoglobin level than that with iron alone in young healthy women: a randomized, double-blind, parallel-group, comparative study.European journal of nutrition · 2023Trial
- Egg Powder Fortification of Tom Brown Significantly Improves Hemoglobin and Ferritin and Reduces Inflammation Among School-Aged Children in Ghana: A Randomized Controlled Trial.Nutrition and metabolic insights · 2026Article
- HRI protein kinase in cytoplasmic heme sensing and mitochondrial stress response: Relevance to hematological and mitochondrial diseases.The Journal of biological chemistry · 2025Review
- Ancient genomic linkage of α-globin and Nprl3 couples metabolism with erythropoiesis.Nature communications · 2025Article
- Mutations in linker-2 of KLF1 impair expression of membrane transporters and cytoskeletal proteins causing hemolysis.Nature communications · 2024Article
- ATF4 in cellular stress, ferroptosis, and cancer.Archives of toxicology · 2024Review
- Metabolic regulation of erythrocyte development and disorders.Experimental hematology · 2024Article
- Ancient genomic linkage couples metabolism with erythroid development.bioRxiv : the preprint server for biology · 2023Article
- Loss of miR-144/451 alleviates β-thalassemia by stimulating ULK1-mediated autophagy of free α-globin.Blood · 2023Article
- Possible-sarcopenic screening with disturbed plasma amino acid profile in the elderly.BMC geriatrics · 2023Article
- Arginine metabolism regulates human erythroid differentiation through hypusination of eIF5A.Blood · 2023Article
- Contribution of the L-Type Amino Acid Transporter Family in the Diagnosis and Treatment of Prostate Cancer.International journal of molecular sciences · 2023Review
- Regulation of eIF4E guides a unique translational program to control erythroid maturation.Science advances · 2022Article
- The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Ribosome-Directed Therapies in Cancer.Biomedicines · 2022Review
- Chiral resolution of plasma amino acids reveals enantiomer-selective associations with organ functions.Amino acids · 2022Article
- Gut microbiome and metabolites: The potential key roles in pulmonary fibrosis.Frontiers in microbiology · 2022Review
- Using the Zebrafish as a Genetic Model to Study Erythropoiesis.International journal of molecular sciences · 2021Review
- Article
- Measurement of labile and protein-bound heme in fixed prostate cancer cells and in cellular fractions.STAR protocols · 2021Article
Corrections and comments
- Commented on by
Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
In multicellular organisms, the mechanisms by which diverse cell types acquire distinct amino acids and how cellular function adapts to their availability are fundamental questions in biology. We found that increased neutral essential amino acid (NEAA) uptake was a critical component of erythropoiesis. As red blood cells matured, expression of the amino acid transporter gene Lat3 increased, which increased NEAA import. Inadequate NEAA uptake by pharmacologic inhibition or RNAi-mediated knockdown of LAT3 triggered a specific reduction in hemoglobin production in zebrafish embryos and murine erythroid cells through the mTORC1 (mammalian target of rapamycin complex 1)/4E-BP (eukaryotic translation initiation factor 4E-binding protein) pathway. CRISPR-mediated deletion of members of the 4E-BP family in murine erythroid cells rendered them resistant to mTORC1 and LAT3 inhibition and restored hemoglobin production. These results identify a developmental role for LAT3 in red blood cells and demonstrate that mTORC1 serves as a homeostatic sensor that couples hemoglobin production at the translational level to sufficient uptake of NEAAs, particularly L-leucine.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.