Cargo-selective regulation of clathrin-mediated endocytosis by AMP-activated protein kinase
Summary: The cell surface abundance of many proteins is controlled by clathrin-mediated endocytosis (CME). CME is driven by the assembly of clathrin and other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). Regulation of CCP dynamics allows for control of the f...
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| Language: | English |
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Elsevier
2025-08-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225013926 |
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| author | Laura A. Orofiamma Ralph Christian Delos Santos Ayshin Mehrabi Nikol Leshchyshyn Geoffrey G. Hesketh Sadia Rahmani Aesha Patel Farnaz Fekri Rehman Ata Colin D.H. Ratcliffe Mathieu J.F. Crupi Lois Mulligan Morag Park Anne-Claude Gingras Costin N. Antonescu |
| author_facet | Laura A. Orofiamma Ralph Christian Delos Santos Ayshin Mehrabi Nikol Leshchyshyn Geoffrey G. Hesketh Sadia Rahmani Aesha Patel Farnaz Fekri Rehman Ata Colin D.H. Ratcliffe Mathieu J.F. Crupi Lois Mulligan Morag Park Anne-Claude Gingras Costin N. Antonescu |
| author_sort | Laura A. Orofiamma |
| collection | DOAJ |
| description | Summary: The cell surface abundance of many proteins is controlled by clathrin-mediated endocytosis (CME). CME is driven by the assembly of clathrin and other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). Regulation of CCP dynamics allows for control of the function of specific cell surface proteins, impacting a range of cellular outcomes. AMP-activated protein kinase (AMPK) becomes activated upon metabolic insufficiency and facilitates cellular adaptation to nutrient stress. Here, we examined how AMPK regulates CME and the cell surface membrane traffic of β1-integrin. We find that AMPK controls CCP dynamics and regulates the abundance of the endocytic adaptor protein Dab2 within CCPs in a manner that requires the GTPase Arf6, thus selectively promoting the CCP recruitment and internalization of β1-integrin. This study reveals a signaling pathway for cargo-selective metabolic regulation of CME by AMPK that impacts the function of cell surface proteins such as integrins. |
| format | Article |
| id | doaj-art-3ff72307255c4639817cfdb9b261b013 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-3ff72307255c4639817cfdb9b261b0132025-08-20T04:00:34ZengElsevieriScience2589-00422025-08-0128811313110.1016/j.isci.2025.113131Cargo-selective regulation of clathrin-mediated endocytosis by AMP-activated protein kinaseLaura A. Orofiamma0Ralph Christian Delos Santos1Ayshin Mehrabi2Nikol Leshchyshyn3Geoffrey G. Hesketh4Sadia Rahmani5Aesha Patel6Farnaz Fekri7Rehman Ata8Colin D.H. Ratcliffe9Mathieu J.F. Crupi10Lois Mulligan11Morag Park12Anne-Claude Gingras13Costin N. Antonescu14Department of Chemistry and Biology, Toronto Metropolitan University, Toronto, ON, Canada; Graduate Program in Molecular Science, Toronto Metropolitan University, Toronto, ON, CanadaDepartment of Chemistry and Biology, Toronto Metropolitan University, Toronto, ON, Canada; Graduate Program in Molecular Science, Toronto Metropolitan University, Toronto, ON, CanadaDepartment of Chemistry and Biology, Toronto Metropolitan University, Toronto, ON, CanadaDepartment of Chemistry and Biology, Toronto Metropolitan University, Toronto, ON, Canada; Graduate Program in Molecular Science, Toronto Metropolitan University, Toronto, ON, CanadaCentre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, CanadaDepartment of Chemistry and Biology, Toronto Metropolitan University, Toronto, ON, Canada; Graduate Program in Molecular Science, Toronto Metropolitan University, Toronto, ON, CanadaDepartment of Chemistry and Biology, Toronto Metropolitan University, Toronto, ON, CanadaDepartment of Chemistry and Biology, Toronto Metropolitan University, Toronto, ON, Canada; Graduate Program in Molecular Science, Toronto Metropolitan University, Toronto, ON, CanadaDepartment of Chemistry and Biology, Toronto Metropolitan University, Toronto, ON, Canada; Graduate Program in Molecular Science, Toronto Metropolitan University, Toronto, ON, CanadaDepartment of Biochemistry, McGill University, Montreal, QC, Canada; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC, CanadaDivision of Cancer Biology and Genetics, Sinclair Cancer Research Institute, and Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON, CanadaDivision of Cancer Biology and Genetics, Sinclair Cancer Research Institute, and Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON, CanadaDepartment of Biochemistry, McGill University, Montreal, QC, Canada; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC, CanadaCentre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, CanadaDepartment of Chemistry and Biology, Toronto Metropolitan University, Toronto, ON, Canada; Graduate Program in Molecular Science, Toronto Metropolitan University, Toronto, ON, Canada; Corresponding authorSummary: The cell surface abundance of many proteins is controlled by clathrin-mediated endocytosis (CME). CME is driven by the assembly of clathrin and other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). Regulation of CCP dynamics allows for control of the function of specific cell surface proteins, impacting a range of cellular outcomes. AMP-activated protein kinase (AMPK) becomes activated upon metabolic insufficiency and facilitates cellular adaptation to nutrient stress. Here, we examined how AMPK regulates CME and the cell surface membrane traffic of β1-integrin. We find that AMPK controls CCP dynamics and regulates the abundance of the endocytic adaptor protein Dab2 within CCPs in a manner that requires the GTPase Arf6, thus selectively promoting the CCP recruitment and internalization of β1-integrin. This study reveals a signaling pathway for cargo-selective metabolic regulation of CME by AMPK that impacts the function of cell surface proteins such as integrins.http://www.sciencedirect.com/science/article/pii/S2589004225013926BiochemistryCell biology |
| spellingShingle | Laura A. Orofiamma Ralph Christian Delos Santos Ayshin Mehrabi Nikol Leshchyshyn Geoffrey G. Hesketh Sadia Rahmani Aesha Patel Farnaz Fekri Rehman Ata Colin D.H. Ratcliffe Mathieu J.F. Crupi Lois Mulligan Morag Park Anne-Claude Gingras Costin N. Antonescu Cargo-selective regulation of clathrin-mediated endocytosis by AMP-activated protein kinase iScience Biochemistry Cell biology |
| title | Cargo-selective regulation of clathrin-mediated endocytosis by AMP-activated protein kinase |
| title_full | Cargo-selective regulation of clathrin-mediated endocytosis by AMP-activated protein kinase |
| title_fullStr | Cargo-selective regulation of clathrin-mediated endocytosis by AMP-activated protein kinase |
| title_full_unstemmed | Cargo-selective regulation of clathrin-mediated endocytosis by AMP-activated protein kinase |
| title_short | Cargo-selective regulation of clathrin-mediated endocytosis by AMP-activated protein kinase |
| title_sort | cargo selective regulation of clathrin mediated endocytosis by amp activated protein kinase |
| topic | Biochemistry Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225013926 |
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