PARP1-mediated PARylation activity is essential for oligodendroglial differentiation and CNS myelination
Summary: The function of poly(ADP-ribosyl) polymerase 1 (PARP1) in myelination and remyelination of the central nervous system (CNS) remains enigmatic. Here, we report that PARP1 is an intrinsic driver for oligodendroglial development and myelination. Genetic PARP1 depletion impairs the differentiat...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-10-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721011426 |
| _version_ | 1818718683945500672 |
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| author | Yan Wang Yanhong Zhang Sheng Zhang Bokyung Kim Vanessa L. Hull Jie Xu Preeti Prabhu Maria Gregory Veronica Martinez-Cerdeno Xinhua Zhan Wenbin Deng Fuzheng Guo |
| author_facet | Yan Wang Yanhong Zhang Sheng Zhang Bokyung Kim Vanessa L. Hull Jie Xu Preeti Prabhu Maria Gregory Veronica Martinez-Cerdeno Xinhua Zhan Wenbin Deng Fuzheng Guo |
| author_sort | Yan Wang |
| collection | DOAJ |
| description | Summary: The function of poly(ADP-ribosyl) polymerase 1 (PARP1) in myelination and remyelination of the central nervous system (CNS) remains enigmatic. Here, we report that PARP1 is an intrinsic driver for oligodendroglial development and myelination. Genetic PARP1 depletion impairs the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes and impedes CNS myelination. Mechanistically, PARP1-mediated PARylation activity is not only necessary but also sufficient for OPC differentiation. At the molecular level, we identify the RNA-binding protein Myef2 as a PARylated target, which controls OPC differentiation through the PARylation-modulated derepression of myelin protein expression. Furthermore, PARP1’s enzymatic activity is necessary for oligodendrocyte and myelin regeneration after demyelination. Together, our findings suggest that PARP1-mediated PARylation activity may be a potential therapeutic target for promoting OPC differentiation and remyelination in neurological disorders characterized by arrested OPC differentiation and remyelination failure such as multiple sclerosis. |
| first_indexed | 2024-12-17T19:54:57Z |
| format | Article |
| id | doaj.art-4c1979ff9c634047baf98a615a1936c5 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-17T19:54:57Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4c1979ff9c634047baf98a615a1936c52022-12-21T21:34:37ZengElsevierCell Reports2211-12472021-10-01371109695PARP1-mediated PARylation activity is essential for oligodendroglial differentiation and CNS myelinationYan Wang0Yanhong Zhang1Sheng Zhang2Bokyung Kim3Vanessa L. Hull4Jie Xu5Preeti Prabhu6Maria Gregory7Veronica Martinez-Cerdeno8Xinhua Zhan9Wenbin Deng10Fuzheng Guo11Department of Neurology, School of Medicine, University of California, Davis, Davis, CA 95817, USA; Institute for Pediatric Regenerative Medicine (IPRM), Shriners Hospitals for Children, Sacramento, CA 95817, USADepartment of Neurology, School of Medicine, University of California, Davis, Davis, CA 95817, USA; Institute for Pediatric Regenerative Medicine (IPRM), Shriners Hospitals for Children, Sacramento, CA 95817, USADepartment of Neurology, School of Medicine, University of California, Davis, Davis, CA 95817, USA; Institute for Pediatric Regenerative Medicine (IPRM), Shriners Hospitals for Children, Sacramento, CA 95817, USADepartment of Neurology, School of Medicine, University of California, Davis, Davis, CA 95817, USA; Institute for Pediatric Regenerative Medicine (IPRM), Shriners Hospitals for Children, Sacramento, CA 95817, USADepartment of Neurology, School of Medicine, University of California, Davis, Davis, CA 95817, USA; Institute for Pediatric Regenerative Medicine (IPRM), Shriners Hospitals for Children, Sacramento, CA 95817, USAInstitute for Pediatric Regenerative Medicine (IPRM), Shriners Hospitals for Children, Sacramento, CA 95817, USADepartment of Neurology, School of Medicine, University of California, Davis, Davis, CA 95817, USA; Institute for Pediatric Regenerative Medicine (IPRM), Shriners Hospitals for Children, Sacramento, CA 95817, USADepartment of Neurology, School of Medicine, University of California, Davis, Davis, CA 95817, USA; Institute for Pediatric Regenerative Medicine (IPRM), Shriners Hospitals for Children, Sacramento, CA 95817, USADepartment of Pathology and Laboratory Medicine, University of California, Davis, Davis, CA 95817, USA; Institute for Pediatric Regenerative Medicine (IPRM), Shriners Hospitals for Children, Sacramento, CA 95817, USADepartment of Neurology, School of Medicine, University of California, Davis, Davis, CA 95817, USABiochemistry and Molecular Medicine, School of Medicine, University of California, Davis, CA 95817, USADepartment of Neurology, School of Medicine, University of California, Davis, Davis, CA 95817, USA; Institute for Pediatric Regenerative Medicine (IPRM), Shriners Hospitals for Children, Sacramento, CA 95817, USA; Corresponding authorSummary: The function of poly(ADP-ribosyl) polymerase 1 (PARP1) in myelination and remyelination of the central nervous system (CNS) remains enigmatic. Here, we report that PARP1 is an intrinsic driver for oligodendroglial development and myelination. Genetic PARP1 depletion impairs the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes and impedes CNS myelination. Mechanistically, PARP1-mediated PARylation activity is not only necessary but also sufficient for OPC differentiation. At the molecular level, we identify the RNA-binding protein Myef2 as a PARylated target, which controls OPC differentiation through the PARylation-modulated derepression of myelin protein expression. Furthermore, PARP1’s enzymatic activity is necessary for oligodendrocyte and myelin regeneration after demyelination. Together, our findings suggest that PARP1-mediated PARylation activity may be a potential therapeutic target for promoting OPC differentiation and remyelination in neurological disorders characterized by arrested OPC differentiation and remyelination failure such as multiple sclerosis.http://www.sciencedirect.com/science/article/pii/S2211124721011426PARP1PARylationPARGoligodendrocytes (OLs)oligodendrocyte progenitor cells (OPCs)myelination |
| spellingShingle | Yan Wang Yanhong Zhang Sheng Zhang Bokyung Kim Vanessa L. Hull Jie Xu Preeti Prabhu Maria Gregory Veronica Martinez-Cerdeno Xinhua Zhan Wenbin Deng Fuzheng Guo PARP1-mediated PARylation activity is essential for oligodendroglial differentiation and CNS myelination Cell Reports PARP1 PARylation PARG oligodendrocytes (OLs) oligodendrocyte progenitor cells (OPCs) myelination |
| title | PARP1-mediated PARylation activity is essential for oligodendroglial differentiation and CNS myelination |
| title_full | PARP1-mediated PARylation activity is essential for oligodendroglial differentiation and CNS myelination |
| title_fullStr | PARP1-mediated PARylation activity is essential for oligodendroglial differentiation and CNS myelination |
| title_full_unstemmed | PARP1-mediated PARylation activity is essential for oligodendroglial differentiation and CNS myelination |
| title_short | PARP1-mediated PARylation activity is essential for oligodendroglial differentiation and CNS myelination |
| title_sort | parp1 mediated parylation activity is essential for oligodendroglial differentiation and cns myelination |
| topic | PARP1 PARylation PARG oligodendrocytes (OLs) oligodendrocyte progenitor cells (OPCs) myelination |
| url | http://www.sciencedirect.com/science/article/pii/S2211124721011426 |
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