Oligodendrocyte precursor cells facilitate neuronal lysosome release
Abstract Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neur...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56484-8 |
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| author | Li-Pao Fang Ching-Hsin Lin Yasser Medlej Renping Zhao Hsin-Fang Chang Qilin Guo Zhonghao Wu Yixun Su Na Zhao Davide Gobbo Amanda Wyatt Vanessa Wahl Frederic Fiore Szu-Min Tu Ulrich Boehm Wenhui Huang Shan Bian Amit Agarwal Marcel A. Lauterbach Chenju Yi Jianqin Niu Anja Scheller Frank Kirchhoff Xianshu Bai |
| author_facet | Li-Pao Fang Ching-Hsin Lin Yasser Medlej Renping Zhao Hsin-Fang Chang Qilin Guo Zhonghao Wu Yixun Su Na Zhao Davide Gobbo Amanda Wyatt Vanessa Wahl Frederic Fiore Szu-Min Tu Ulrich Boehm Wenhui Huang Shan Bian Amit Agarwal Marcel A. Lauterbach Chenju Yi Jianqin Niu Anja Scheller Frank Kirchhoff Xianshu Bai |
| author_sort | Li-Pao Fang |
| collection | DOAJ |
| description | Abstract Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neuronal lysosomes. A reduction in the number or branching of OPCs reduces these contacts, which is associated with lysosome accumulation and altered metabolism in neurons and more senescent neurons with age. A similar reduction in OPC branching and neuronal lysosome accumulation is seen in an early-stage mouse model of Alzheimer’s disease. Our findings have implications for the prevention of age-related pathologies and the treatment of neurodegenerative diseases. |
| format | Article |
| id | doaj-art-49dc4f9b9c734fc3a42706333fd8502c |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-49dc4f9b9c734fc3a42706333fd8502c2025-02-02T12:33:23ZengNature PortfolioNature Communications2041-17232025-01-0116111010.1038/s41467-025-56484-8Oligodendrocyte precursor cells facilitate neuronal lysosome releaseLi-Pao Fang0Ching-Hsin Lin1Yasser Medlej2Renping Zhao3Hsin-Fang Chang4Qilin Guo5Zhonghao Wu6Yixun Su7Na Zhao8Davide Gobbo9Amanda Wyatt10Vanessa Wahl11Frederic Fiore12Szu-Min Tu13Ulrich Boehm14Wenhui Huang15Shan Bian16Amit Agarwal17Marcel A. Lauterbach18Chenju Yi19Jianqin Niu20Anja Scheller21Frank Kirchhoff22Xianshu Bai23Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandCenter for Gender-specific Biology and Medicine (CGBM), University of SaarlandMolecular Imaging, CIPMM, University of SaarlandBiophysics, CIPMM, University of SaarlandCenter for Gender-specific Biology and Medicine (CGBM), University of SaarlandMolecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandResearch Centre, Seventh Affiliated Hospital of Sun Yat-sen UniversityResearch Centre, Seventh Affiliated Hospital of Sun Yat-sen UniversityMolecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandMolecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandCenter for Gender-specific Biology and Medicine (CGBM), University of SaarlandCenter for Gender-specific Biology and Medicine (CGBM), University of SaarlandThe Chica and Heinz Schaller Research Group, Institute for Anatomy and Cell Biology, Heidelberg UniversityCenter for Gender-specific Biology and Medicine (CGBM), University of SaarlandCenter for Gender-specific Biology and Medicine (CGBM), University of SaarlandMolecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandInstitute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityThe Chica and Heinz Schaller Research Group, Institute for Anatomy and Cell Biology, Heidelberg UniversityMolecular Imaging, CIPMM, University of SaarlandDepartment of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical UniversityResearch Centre, Seventh Affiliated Hospital of Sun Yat-sen UniversityMolecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandMolecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandMolecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of SaarlandAbstract Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neuronal lysosomes. A reduction in the number or branching of OPCs reduces these contacts, which is associated with lysosome accumulation and altered metabolism in neurons and more senescent neurons with age. A similar reduction in OPC branching and neuronal lysosome accumulation is seen in an early-stage mouse model of Alzheimer’s disease. Our findings have implications for the prevention of age-related pathologies and the treatment of neurodegenerative diseases.https://doi.org/10.1038/s41467-025-56484-8 |
| spellingShingle | Li-Pao Fang Ching-Hsin Lin Yasser Medlej Renping Zhao Hsin-Fang Chang Qilin Guo Zhonghao Wu Yixun Su Na Zhao Davide Gobbo Amanda Wyatt Vanessa Wahl Frederic Fiore Szu-Min Tu Ulrich Boehm Wenhui Huang Shan Bian Amit Agarwal Marcel A. Lauterbach Chenju Yi Jianqin Niu Anja Scheller Frank Kirchhoff Xianshu Bai Oligodendrocyte precursor cells facilitate neuronal lysosome release Nature Communications |
| title | Oligodendrocyte precursor cells facilitate neuronal lysosome release |
| title_full | Oligodendrocyte precursor cells facilitate neuronal lysosome release |
| title_fullStr | Oligodendrocyte precursor cells facilitate neuronal lysosome release |
| title_full_unstemmed | Oligodendrocyte precursor cells facilitate neuronal lysosome release |
| title_short | Oligodendrocyte precursor cells facilitate neuronal lysosome release |
| title_sort | oligodendrocyte precursor cells facilitate neuronal lysosome release |
| url | https://doi.org/10.1038/s41467-025-56484-8 |
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