Distinct phosphorylation states of mammalian CaMKIIβ control the induction and maintenance of sleep
Fig 2
Perturbation on the kinase activity of CaMKII affects sleep duration.
(A) Schematic diagram of CaMKIIβ activation via deletion of its C-terminus. Deletion of the regulatory segment and linker region exposes the kinase domain of the CaMKIIβ and makes the enzyme constitutively activated. (B, C) Sleep/wake parameters (B) and sleep profiles (C) of mice expressing the CaMKIIβ del mutant, averaged over 6 days. The shaded areas represent SEM. Multiple comparison tests were performed between all individual groups. (D) Schematic diagram of CaMKII inhibition by AIP2 expression. AIP2 competitively binds to the kinase domain and inhibits substrate phosphorylation. (E, F) Sleep/wake parameters (E) and sleep profiles (F) of mice expressing AIP2 or the RARA mutant measured by the SSS, averaged over 6 days. PBS: PBS-injected mice (n = 6). (G-I) Sleep phenotypes (G and I) and sleep profiles (H) of mice expressing AIP2 or the RARA mutant measured by EEG/EMG recordings. (J) Differences in transition probabilities (between wakefulness (W), NREM sleep (N), and REM sleep (R)) between mice expressing AIP2 or the RARA mutant. Magenta lines and dashed blue lines indicate when the values for the AIP2-expressing mice are significantly (p < 0.05) higher and lower, respectively. The underlying data can be found in S1 Data. Error bars: SEM, *p < 0.05, **p < 0.01, ***p < 0.001, n.s.: no significance. See also S6–S8 Figs. AIP2, autocamtide inhibitory peptide 2; CaM, calmodulin; CaMKII, calmodulin-dependent protein kinase II; del, deletion; EEG, electroencephalogram; EMG, electromyogram; hSyn1, human synapsin-1; NREM, nonrapid eye movement; REM, rapid eye movement; SSS, snappy sleep stager; WT, wild-type; ZT, zeitgeber time.