Distinct phosphorylation states of mammalian CaMKIIß control the induction and maintenance of sleep.
PLoS Biol
; 20(10): e3001813, 2022 10.
Article
de En
| MEDLINE
| ID: mdl-36194579
ABSTRACT
The reduced sleep duration previously observed in Camk2b knockout mice revealed a role for Ca2+/calmodulin-dependent protein kinase II (CaMKII)ß as a sleep-promoting kinase. However, the underlying mechanism by which CaMKIIß supports sleep regulation is largely unknown. Here, we demonstrate that activation or inhibition of CaMKIIß can increase or decrease sleep duration in mice by almost 2-fold, supporting the role of CaMKIIß as a core sleep regulator in mammals. Importantly, we show that this sleep regulation depends on the kinase activity of CaMKIIß. A CaMKIIß mutant mimicking the constitutive-active (auto)phosphorylation state promotes the transition from awake state to sleep state, while mutants mimicking subsequent multisite (auto)phosphorylation states suppress the transition from sleep state to awake state. These results suggest that the phosphorylation states of CaMKIIß differently control sleep induction and maintenance processes, leading us to propose a "phosphorylation hypothesis of sleep" for the molecular control of sleep in mammals.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Calcium
/
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Limites:
Animals
Langue:
En
Journal:
PLoS Biol
Sujet du journal:
BIOLOGIA
Année:
2022
Type de document:
Article
Pays d'affiliation:
Japon