ArticleCell death and differentiation2014
The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 57 citations in OpenAlex.
- GATOR2 regulates the nutrient-dependent recruitment of GATOR1 to lysosomes.bioRxiv : the preprint server for biology · 2026Article
- Feeding a rich diet supplemented with the translation inhibitor cycloheximide decreases lifespan and ovary size in Drosophila.Biology open · 2024Article
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- Feeding a rich diet supplemented with the translation inhibitor cycloheximide decreases lifespan and ovary size in Drosophila.bioRxiv : the preprint server for biology · 2024Article
- NPRL2 is required for proliferation of oncogenic Ras-transformed bronchial epithelial cells.Cell division · 2024Article
- An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway.Nature communications · 2024Article
- Finishing the egg.Genetics · 2024Article
- mTORC1 is required for differentiation of germline stem cells in the Drosophila melanogaster testis.PloS one · 2024Article
- Differential amino acid transporter expression in adultmicroPublication biology · 2024Article
- Refining the electroclinical spectrum of NPRL3-related epilepsy: A novel multiplex family and literature review.Epilepsia open · 2023Review
- An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway.bioRxiv : the preprint server for biology · 2023Article
- A key gene for the climatic adaptation of Apis cerana populations in China according to selective sweep analysis.BMC genomics · 2023Article
- Wdr59 promotes or inhibits TORC1 activity depending on cellular context.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
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- Lysosomal cystine mobilization shapes the response of TORC1 and tissue growth to fasting.Science (New York, N.Y.) · 2022Article
- FKBP39 controls nutrient dependent Nprl3 expression and TORC1 activity in Drosophila.Cell death & disease · 2021Article
- Positive selection alone is sufficient for whole genome differentiation at the early stage of speciation process in the fall armyworm.BMC evolutionary biology · 2020Article
- The Rag GTPase Regulates the Dynamic Behavior of TSC Downstream of Both Amino Acid and Growth Factor Restriction.Developmental cell · 2020Article
- Royal jelly attenuates metabolic defects in aBiology open · 2020Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Target of rapamycin complex 1 (TORC1) is a master regulator of metabolism in eukaryotes that integrates information from multiple upstream signaling pathways. In yeast, the Nitrogen permease regulators 2 and 3 (Npr2 and Npr3) mediate an essential response to amino-acid limitation upstream of TORC1. In mammals, the Npr2 ortholog, Nprl2, is a putative tumor suppressor gene that inhibits cell growth and enhances sensitivity to numerous anticancer drugs including cisplatin. However, the precise role of Nprl2 and Nprl3 in the regulation of metabolism in metazoans remains poorly defined. Here we demonstrate that the central importance of Nprl2 and Nprl3 in the response to amino-acid starvation has been conserved from single celled to multicellular animals. We find that in Drosophila Nprl2 and Nprl3 physically interact and are targeted to lysosomes and autolysosomes. Using oogenesis as a model system, we show that Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation. Moreover, the inhibition TORC1 by Nprl2/3 is critical to the preservation of female fertility during times of protein scarcity. In young egg chambers the failure to downregulate TORC1 in response to amino-acid limitation triggers apoptosis. Thus, our data suggest the presence of a metabolic checkpoint that initiates a cell death program when TORC1 activity remains inappropriately high during periods of amino-acid and/or nutrient scarcity in oogenesis. Finally, we demonstrate that Nprl2/3 work in concert with the TORC1 inhibitors Tsc1/2 to fine tune TORC1 activity during oogenesis and that Tsc1 is a critical downstream effector of Akt1 in the female germline.
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