An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway
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 signa...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46680-3 |
| _version_ | 1797247160697225216 |
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| author | Grace Y. Liu Patrick Jouandin Raymond E. Bahng Norbert Perrimon David M. Sabatini |
| author_facet | Grace Y. Liu Patrick Jouandin Raymond E. Bahng Norbert Perrimon David M. Sabatini |
| author_sort | Grace Y. Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T19:54:17Z |
| format | Article |
| id | doaj.art-cfc0b44a13e543eb9b38d60685f127f0 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T19:54:17Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-cfc0b44a13e543eb9b38d60685f127f02024-03-24T12:26:44ZengNature PortfolioNature Communications2041-17232024-03-0115111610.1038/s41467-024-46680-3An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathwayGrace Y. Liu0Patrick Jouandin1Raymond E. Bahng2Norbert Perrimon3David M. Sabatini4Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of BiologyDepartment of Genetics, Blavatnik Institute, Harvard Medical SchoolWhitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of BiologyDepartment of Genetics, Blavatnik Institute, Harvard Medical SchoolInstitute of Organic Chemistry and BiochemistryAbstract 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.https://doi.org/10.1038/s41467-024-46680-3 |
| spellingShingle | Grace Y. Liu Patrick Jouandin Raymond E. Bahng Norbert Perrimon David M. Sabatini An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway Nature Communications |
| title | An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway |
| title_full | An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway |
| title_fullStr | An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway |
| title_full_unstemmed | An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway |
| title_short | An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway |
| title_sort | evolutionary mechanism to assimilate new nutrient sensors into the mtorc1 pathway |
| url | https://doi.org/10.1038/s41467-024-46680-3 |
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