| First Author | Zhou S | Year | 2025 |
| Journal | Commun Biol | Volume | 8 |
| Issue | 1 | Pages | 1018 |
| PubMed ID | 40628956 | Mgi Jnum | J:375173 |
| Mgi Id | MGI:8220974 | Doi | 10.1038/s42003-025-08437-6 |
| Citation | Zhou S, et al. (2025) PP2Acalpha regulates sleep amount and sleep homeostasis in mice. Commun Biol 8(1):1018 |
| abstractText | 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-PP2Acalpha and PP2Acbeta-in sleep regulation in male mice. Adult brain chimeric (ABC) knockout of PP2Acalpha, but not PP2Acbeta, across mouse brain neurons reduces daily amount of rapid eye movement (REM) and non-REM (NREM) sleep, but elevates NREM delta power. Additionally, ABC-PP2Acalpha(KO) diminishes and delays homeostatic recovery NREM sleep after sleep deprivation. ABC-expression of wild-type PP2Acalpha or PP2Acbeta, but not methylation deficient mutant PP2Acalpha, rescues the sleep phenotypes of ABC-PP2Acalpha(KappaOmicron) mice. Moreover, selective knockout of PP2Acalpha in CaMKII(+) or Vglut2(+) neurons, but not in mDlx(+) or Vgat(+) neurons, recapitulates ABC-PP2Acalpha(KO) sleep phenotypes. These results identify PP2Acalpha as a key regulator of sleep amount and sleep homeostasis mainly in the excitatory neurons, and suggest that methylation of PP2Acalpha is critical for its sleep functions. |
