ArticleNature communications2024
An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Modulation of Stress and Anabolic Signalling Pathways by Whey Protein Isolate in C2C12 Cells Under Exercise-Mimetic Conditions.Biomedicines · 2026Article
- mTOR signaling regulates demand-adapted hematopoiesis and metabolic reprogramming required for an effective cellular immune response in Drosophila melanogaster larvae.PLoS genetics · 2026Article
- Structure and function of the yeast amino acid-sensing SEAC-EGOC supercomplex.Nature structural & molecular biology · 2026Article
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Article
- mTORC1 senses glutamine and other amino acids through GCN2.The EMBO journal · 2025Article
- The Molecular Basis of Amino Acids Sensing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- S-adenosylmethionine metabolism buffering is regulated by a decrease in glycine N-methyltransferase via the nuclear ubiquitin-proteasome system.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- An insulin-sensitive Drosophila insulin-like receptor mutant remodels methionine metabolism to extend lifespan.PLoS genetics · 2025Article
- Masterful macrophages: understanding and targeting activation dysfunction in diabetic wounds.Burns & trauma · 2025Review
- Review
- Closing in on human methylation-the versatile family of seven-β-strand (METTL) methyltransferases.Nucleic acids research · 2024Review
- Eukaryotic cell size regulation and its implications for cellular function and dysfunction.Physiological reviews · 2024Review
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Animals sense and respond to nutrient availability in their environments, a task coordinated in part by the mTOR complex 1 (mTORC1) pathway. mTORC1 regulates growth in response to nutrients and, in mammals, senses specific amino acids through specialized sensors that bind the GATOR1/2 signaling hub. Given that animals can occupy diverse niches, we hypothesized that the pathway might evolve distinct sensors in different metazoan phyla. Whether such customization occurs, and how the mTORC1 pathway might capture new inputs, is unknown. Here, we identify the Drosophila melanogaster protein Unmet expectations (CG11596) as a species-restricted methionine sensor that directly binds the fly GATOR2 complex in a fashion antagonized by S-adenosylmethionine (SAM). We find that in Dipterans GATOR2 rapidly evolved the capacity to bind Unmet and to thereby repurpose a previously independent methyltransferase as a SAM sensor. Thus, the modular architecture of the mTORC1 pathway allows it to co-opt preexisting enzymes to expand its nutrient sensing capabilities, revealing a mechanism for conferring evolvability on an otherwise conserved system.
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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.