RER1 regulates lipid metabolism in monocytes and macrophages
Abstract Retention in endoplasmic reticulum sorting receptor 1 (RER1) mediates the retention and retrieval of select cargo proteins, and thereby regulates protein transport in the secretory pathway and assembly of distinct protein complexes. Recently, RER1 was implicated in the assembly and subcellu...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2025-08-01
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| Series: | Cellular and Molecular Life Sciences |
| Online Access: | https://doi.org/10.1007/s00018-025-05817-3 |
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| author | Yanxia Liu Sandra Theil Mohamed H. Yaghmour Anja Kerksiek Peng Chen Ingo G.H. Schmidt-Wolf Rebecca Barker Eva Bartok Dieter Lütjohann Christoph Thiele Jochen Walter |
| author_facet | Yanxia Liu Sandra Theil Mohamed H. Yaghmour Anja Kerksiek Peng Chen Ingo G.H. Schmidt-Wolf Rebecca Barker Eva Bartok Dieter Lütjohann Christoph Thiele Jochen Walter |
| author_sort | Yanxia Liu |
| collection | DOAJ |
| description | Abstract Retention in endoplasmic reticulum sorting receptor 1 (RER1) mediates the retention and retrieval of select cargo proteins, and thereby regulates protein transport in the secretory pathway and assembly of distinct protein complexes. Recently, RER1 was implicated in the assembly and subcellular transport of the TREM2-DAP12 immune receptor complex, and its function in intracellular signaling and phagocytosis. However, the role of RER1 in the regulation of immune cell metabolism remained unknown. Here, we demonstrate an important role of RER1 in the lipid metabolism of monocytic and macrophage-like differentiated THP-1 cells. The deficiency of RER1 resulted in the accumulation of lipid droplets (LDs) in both monocytes and macrophage-like cells. Comprehensive mass spectrometry analyses revealed complex changes in the cellular lipid metabolism and the composition of LDs. RNA sequencing revealed an important role of RER1 in the regulation of genes related to lipid metabolism. Further, western immunoblotting confirmed an important role of RER1 in the expression of select key proteins involved in cellular lipid metabolism. The combined data indicate that RER1 plays an essential role in lipid metabolism in monocytes and macrophages. |
| format | Article |
| id | doaj-art-49e5cd85bb43450da5382ee85eaabe75 |
| institution | Kabale University |
| issn | 1420-9071 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Springer |
| record_format | Article |
| series | Cellular and Molecular Life Sciences |
| spelling | doaj-art-49e5cd85bb43450da5382ee85eaabe752025-08-20T03:42:40ZengSpringerCellular and Molecular Life Sciences1420-90712025-08-0182111910.1007/s00018-025-05817-3RER1 regulates lipid metabolism in monocytes and macrophagesYanxia Liu0Sandra Theil1Mohamed H. Yaghmour2Anja Kerksiek3Peng Chen4Ingo G.H. Schmidt-Wolf5Rebecca Barker6Eva Bartok7Dieter Lütjohann8Christoph Thiele9Jochen Walter10Center of Neurology, University Hospital BonnCenter of Neurology, University Hospital BonnLIMES Life and Medical Sciences Institute, University of BonnInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital BonnDepartment of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital BonnDepartment of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital BonnInstitute of Experimental Hematology and Transfusion Medicine, University Hospital BonnInstitute of Experimental Hematology and Transfusion Medicine, University Hospital BonnInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital BonnLIMES Life and Medical Sciences Institute, University of BonnCenter of Neurology, University Hospital BonnAbstract Retention in endoplasmic reticulum sorting receptor 1 (RER1) mediates the retention and retrieval of select cargo proteins, and thereby regulates protein transport in the secretory pathway and assembly of distinct protein complexes. Recently, RER1 was implicated in the assembly and subcellular transport of the TREM2-DAP12 immune receptor complex, and its function in intracellular signaling and phagocytosis. However, the role of RER1 in the regulation of immune cell metabolism remained unknown. Here, we demonstrate an important role of RER1 in the lipid metabolism of monocytic and macrophage-like differentiated THP-1 cells. The deficiency of RER1 resulted in the accumulation of lipid droplets (LDs) in both monocytes and macrophage-like cells. Comprehensive mass spectrometry analyses revealed complex changes in the cellular lipid metabolism and the composition of LDs. RNA sequencing revealed an important role of RER1 in the regulation of genes related to lipid metabolism. Further, western immunoblotting confirmed an important role of RER1 in the expression of select key proteins involved in cellular lipid metabolism. The combined data indicate that RER1 plays an essential role in lipid metabolism in monocytes and macrophages.https://doi.org/10.1007/s00018-025-05817-3 |
| spellingShingle | Yanxia Liu Sandra Theil Mohamed H. Yaghmour Anja Kerksiek Peng Chen Ingo G.H. Schmidt-Wolf Rebecca Barker Eva Bartok Dieter Lütjohann Christoph Thiele Jochen Walter RER1 regulates lipid metabolism in monocytes and macrophages Cellular and Molecular Life Sciences |
| title | RER1 regulates lipid metabolism in monocytes and macrophages |
| title_full | RER1 regulates lipid metabolism in monocytes and macrophages |
| title_fullStr | RER1 regulates lipid metabolism in monocytes and macrophages |
| title_full_unstemmed | RER1 regulates lipid metabolism in monocytes and macrophages |
| title_short | RER1 regulates lipid metabolism in monocytes and macrophages |
| title_sort | rer1 regulates lipid metabolism in monocytes and macrophages |
| url | https://doi.org/10.1007/s00018-025-05817-3 |
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