Wnt regulates amino acid transporter Slc7a5 and so constrains the integrated stress response in mouse embryos
| العنوان: | Wnt regulates amino acid transporter Slc7a5 and so constrains the integrated stress response in mouse embryos |
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| المؤلفون: | Gail Singer, Terry P Yamaguchi, Alwyn Dady, Yun-Bo Shi, Nadège Poncet, Pamela A. Halley, Peter M. Taylor, Melanie Febrer, Kate G. Storey, Marek Gierlinski, Christopher Lipina |
| المصدر: | EMBO Reports |
| بيانات النشر: | EMBO, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Slc7a5/Lat1, Morphogenesis, mTORC1, Mechanistic Target of Rapamycin Complex 1, Biology, mouse embryo morphogenesis, Biochemistry, Article, Large Neutral Amino Acid-Transporter 1, Mice, 03 medical and health sciences, Limb bud, 0302 clinical medicine, Gene expression, Genetics, Animals, Integrated stress response, Protein phosphorylation, Amino acid transporter, Membrane & Intracellular Transport, Wnt Signaling Pathway, Molecular Biology, Wnt signalling, Cell Proliferation, 030304 developmental biology, 0303 health sciences, amino acid transport, Wnt signaling pathway, Articles, integrated stress response, Cell biology, Development & Differentiation, 030217 neurology & neurosurgery, Signal Transduction |
| الوصف: | Amino acids are essential for cellular metabolism, and it is important to understand how nutrient supply is coordinated with changing energy requirements during embryogenesis. Here, we show that the amino acid transporter Slc7a5/Lat1 is highly expressed in tissues undergoing morphogenesis and that Slc7a5‐null mouse embryos have profound neural and limb bud outgrowth defects. Slc7a5‐null neural tissue exhibited aberrant mTORC1 activity and cell proliferation; transcriptomics, protein phosphorylation and apoptosis analyses further indicated induction of the integrated stress response as a potential cause of observed defects. The pattern of stress response gene expression induced in Slc7a5‐null embryos was also detected at low level in wild‐type embryos and identified stress vulnerability specifically in tissues undergoing morphogenesis. The Slc7a5‐null phenotype is reminiscent of Wnt pathway mutants, and we show that Wnt/β‐catenin loss inhibits Slc7a5 expression and induces this stress response. Wnt signalling therefore normally supports the metabolic demands of morphogenesis and constrains cellular stress. Moreover, operation in the embryo of the integrated stress response, which is triggered by pathogen‐mediated as well as metabolic stress, may provide a mechanistic explanation for a range of developmental defects. The amino acid transporter Slc7a5 sustains the metabolic demands of tissues undergoing morphogenesis during mouse embryogenesis and so constrains the activation of the integrated stress response. |
| تدمد: | 1469-3178 1469-221X |
| DOI: | 10.15252/embr.201948469 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::04e86eeeb120d6f6d230eb1e5f60108a https://doi.org/10.15252/embr.201948469 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....04e86eeeb120d6f6d230eb1e5f60108a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14693178 1469221X |
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| DOI: | 10.15252/embr.201948469 |