Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function
ATG5 is one of the core autophagy proteins with additional functions such as noncanonical membrane atg8ylation, which among a growing number of biological outputs includes control of tuberculosis in animal models. Here, we show that ATG5 associates with retromer’s core components VPS26, VPS29, and V...
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eLife Sciences Publications Ltd
2025-01-01
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| Online Access: | https://elifesciences.org/articles/100928 |
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| author | Masroor Ahmad Paddar Fulong Wang Einar S Trosdal Emily Hendrix Yi He Michelle R Salemi Michal Mudd Jingyue Jia Thabata Duque Ruheena Javed Brett S Phinney Vojo Deretic |
| author_facet | Masroor Ahmad Paddar Fulong Wang Einar S Trosdal Emily Hendrix Yi He Michelle R Salemi Michal Mudd Jingyue Jia Thabata Duque Ruheena Javed Brett S Phinney Vojo Deretic |
| author_sort | Masroor Ahmad Paddar |
| collection | DOAJ |
| description | ATG5 is one of the core autophagy proteins with additional functions such as noncanonical membrane atg8ylation, which among a growing number of biological outputs includes control of tuberculosis in animal models. Here, we show that ATG5 associates with retromer’s core components VPS26, VPS29, and VPS35 and modulates retromer function. Knockout of ATG5 blocked trafficking of a key glucose transporter sorted by the retromer, GLUT1, to the plasma membrane. Knockouts of other genes essential for membrane atg8ylation, of which ATG5 is a component, affected GLUT1 sorting, indicating that membrane atg8ylation as a process affects retromer function and endosomal sorting. The contribution of membrane atg8ylation to retromer function in GLUT1 sorting was independent of canonical autophagy. These findings expand the scope of membrane atg8ylation to specific sorting processes in the cell dependent on the retromer and its known interactors. |
| format | Article |
| id | doaj-art-401ff80fa3ac48cd97f4c0f4d29ba6e3 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-401ff80fa3ac48cd97f4c0f4d29ba6e32025-01-07T12:45:42ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.100928Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and functionMasroor Ahmad Paddar0https://orcid.org/0009-0008-5639-3006Fulong Wang1Einar S Trosdal2Emily Hendrix3Yi He4Michelle R Salemi5Michal Mudd6Jingyue Jia7Thabata Duque8Ruheena Javed9Brett S Phinney10Vojo Deretic11https://orcid.org/0000-0002-3624-5208Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, Albuquerque, United States; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, United StatesAutophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, Albuquerque, United States; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, United StatesAutophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, Albuquerque, United States; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, United StatesDepartment of Chemistry & Chemical Biology, The University of New Mexico, Albuquerque, United StatesDepartment of Chemistry & Chemical Biology, The University of New Mexico, Albuquerque, United StatesProteomics Core Facility, University of California, Davis, Davis, United StatesAutophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, Albuquerque, United States; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, United StatesAutophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, Albuquerque, United States; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, United StatesAutophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, Albuquerque, United States; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, United StatesAutophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, Albuquerque, United States; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, United StatesProteomics Core Facility, University of California, Davis, Davis, United StatesAutophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, Albuquerque, United States; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, United StatesATG5 is one of the core autophagy proteins with additional functions such as noncanonical membrane atg8ylation, which among a growing number of biological outputs includes control of tuberculosis in animal models. Here, we show that ATG5 associates with retromer’s core components VPS26, VPS29, and VPS35 and modulates retromer function. Knockout of ATG5 blocked trafficking of a key glucose transporter sorted by the retromer, GLUT1, to the plasma membrane. Knockouts of other genes essential for membrane atg8ylation, of which ATG5 is a component, affected GLUT1 sorting, indicating that membrane atg8ylation as a process affects retromer function and endosomal sorting. The contribution of membrane atg8ylation to retromer function in GLUT1 sorting was independent of canonical autophagy. These findings expand the scope of membrane atg8ylation to specific sorting processes in the cell dependent on the retromer and its known interactors.https://elifesciences.org/articles/100928autophagyatg8ylationmembrane transportglucose transportactive tuberculosislatent tuberculosis |
| spellingShingle | Masroor Ahmad Paddar Fulong Wang Einar S Trosdal Emily Hendrix Yi He Michelle R Salemi Michal Mudd Jingyue Jia Thabata Duque Ruheena Javed Brett S Phinney Vojo Deretic Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function eLife autophagy atg8ylation membrane transport glucose transport active tuberculosis latent tuberculosis |
| title | Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function |
| title_full | Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function |
| title_fullStr | Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function |
| title_full_unstemmed | Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function |
| title_short | Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function |
| title_sort | noncanonical roles of atg5 and membrane atg8ylation in retromer assembly and function |
| topic | autophagy atg8ylation membrane transport glucose transport active tuberculosis latent tuberculosis |
| url | https://elifesciences.org/articles/100928 |
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