PP2Acα regulates sleep amount and sleep homeostasis in mice
Abstract Genetic studies in mice have identified multiple sleep-regulating protein kinases, but the sleep functions of protein phosphatases remain largely unclear. Here, we performed adeno-associated virus-mediated somatic genetics analysis of PP2A catalytic subunits–PP2Acα and PP2Acβ–in sleep regul...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08437-6 |
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| _version_ | 1849343617056899072 |
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| author | Shuang Zhou Bihan Shi Lin Chen Xin Yin Minghao Liu Chongyang Wu Haiyan Wang Xia Wang Bin Li Fengchao Wang Qi Li Qinghua Liu |
| author_facet | Shuang Zhou Bihan Shi Lin Chen Xin Yin Minghao Liu Chongyang Wu Haiyan Wang Xia Wang Bin Li Fengchao Wang Qi Li Qinghua Liu |
| author_sort | Shuang Zhou |
| collection | DOAJ |
| description | Abstract Genetic studies in mice have identified multiple sleep-regulating protein kinases, but the sleep functions of protein phosphatases remain largely unclear. Here, we performed adeno-associated virus-mediated somatic genetics analysis of PP2A catalytic subunits–PP2Acα and PP2Acβ–in sleep regulation in male mice. Adult brain chimeric (ABC) knockout of PP2Acα, but not PP2Acβ, across mouse brain neurons reduces daily amount of rapid eye movement (REM) and non-REM (NREM) sleep, but elevates NREM delta power. Additionally, ABC-PP2Acα KO diminishes and delays homeostatic recovery NREM sleep after sleep deprivation. ABC-expression of wild-type PP2Acα or PP2Acβ, but not methylation deficient mutant PP2Acα, rescues the sleep phenotypes of ABC-PP2Acα ΚΟ mice. Moreover, selective knockout of PP2Acα in CaMKII + or Vglut2 + neurons, but not in mDlx + or Vgat + neurons, recapitulates ABC-PP2Acα KO sleep phenotypes. These results identify PP2Acα as a key regulator of sleep amount and sleep homeostasis mainly in the excitatory neurons, and suggest that methylation of PP2Acα is critical for its sleep functions. |
| format | Article |
| id | doaj-art-a7c6a094de1c459f9e0bbf3aafdd2d5b |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-a7c6a094de1c459f9e0bbf3aafdd2d5b2025-08-20T03:42:56ZengNature PortfolioCommunications Biology2399-36422025-07-018111110.1038/s42003-025-08437-6PP2Acα regulates sleep amount and sleep homeostasis in miceShuang Zhou0Bihan Shi1Lin Chen2Xin Yin3Minghao Liu4Chongyang Wu5Haiyan Wang6Xia Wang7Bin Li8Fengchao Wang9Qi Li10Qinghua Liu11School of Life Sciences, Beijing Normal UniversityNational Institute of Biological Sciences, Beijing (NIBS)National Institute of Biological Sciences, Beijing (NIBS)National Institute of Biological Sciences, Beijing (NIBS)National Institute of Biological Sciences, Beijing (NIBS)National Institute of Biological Sciences, Beijing (NIBS)National Institute of Biological Sciences, Beijing (NIBS)National Institute of Biological Sciences, Beijing (NIBS)National Institute of Biological Sciences, Beijing (NIBS)National Institute of Biological Sciences, Beijing (NIBS)National Institute of Biological Sciences, Beijing (NIBS)Tsinghua Institute of Multidisciplinary Biomedical Research (TIMBR), Tsinghua UniversityAbstract Genetic studies in mice have identified multiple sleep-regulating protein kinases, but the sleep functions of protein phosphatases remain largely unclear. Here, we performed adeno-associated virus-mediated somatic genetics analysis of PP2A catalytic subunits–PP2Acα and PP2Acβ–in sleep regulation in male mice. Adult brain chimeric (ABC) knockout of PP2Acα, but not PP2Acβ, across mouse brain neurons reduces daily amount of rapid eye movement (REM) and non-REM (NREM) sleep, but elevates NREM delta power. Additionally, ABC-PP2Acα KO diminishes and delays homeostatic recovery NREM sleep after sleep deprivation. ABC-expression of wild-type PP2Acα or PP2Acβ, but not methylation deficient mutant PP2Acα, rescues the sleep phenotypes of ABC-PP2Acα ΚΟ mice. Moreover, selective knockout of PP2Acα in CaMKII + or Vglut2 + neurons, but not in mDlx + or Vgat + neurons, recapitulates ABC-PP2Acα KO sleep phenotypes. These results identify PP2Acα as a key regulator of sleep amount and sleep homeostasis mainly in the excitatory neurons, and suggest that methylation of PP2Acα is critical for its sleep functions.https://doi.org/10.1038/s42003-025-08437-6 |
| spellingShingle | Shuang Zhou Bihan Shi Lin Chen Xin Yin Minghao Liu Chongyang Wu Haiyan Wang Xia Wang Bin Li Fengchao Wang Qi Li Qinghua Liu PP2Acα regulates sleep amount and sleep homeostasis in mice Communications Biology |
| title | PP2Acα regulates sleep amount and sleep homeostasis in mice |
| title_full | PP2Acα regulates sleep amount and sleep homeostasis in mice |
| title_fullStr | PP2Acα regulates sleep amount and sleep homeostasis in mice |
| title_full_unstemmed | PP2Acα regulates sleep amount and sleep homeostasis in mice |
| title_short | PP2Acα regulates sleep amount and sleep homeostasis in mice |
| title_sort | pp2acα regulates sleep amount and sleep homeostasis in mice |
| url | https://doi.org/10.1038/s42003-025-08437-6 |
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