作者
Jacky Chung, Daniel E Bauer, Alireza Ghamari, Christopher P Nizzi, Kathryn M Deck, Paul D Kingsley, Yvette Y Yien, Nicholas C Huston, Caiyong Chen, Johannes G Wittig, James Palis, Stuart H Orkin, Harvey F Lodish, Richard S Eisenstein, Alan B Cantor, Barry H Paw
发表日期
2014/12/6
来源
Blood, The Journal of the American Society of Hematology
卷号
124
期号
21
页码范围
2660-2660
出版商
American Society of Hematology
简介
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. Here, we find that maturing erythroid cells increase L-leucine uptake via transcriptional up-regulation of the L-leucine transporter, LAT3. Inadequate L-leucine uptake by L-leucine starvation or LAT3 inhibition triggers a specific reduction in hemoglobin production in zebrafish embryos and murine erythroid cells via the mTORC1/4E-BP pathway. CRISPR-mediated deletion of 4E-BPs in murine erythroid cells renders them resistant to mTORC1 and LAT3 inhibition, markedly restoring hemoglobinization. Our complementary results demonstrate that globins are direct translational mTORC1 targets during normal development. This pathway is distinct from the previously reported translational regulatory mechanisms mediated by …