The team found that when SIK3 was lacking or when HDAC4 was modified to prevent phosphorylation, the mice slept less.
In contrast, when the mice had a more active version of SIK3, which increased the phosphorylation of HDAC4, they slept much longer.
They also identified another protein, LKB1, that phosphorylates SIK3, and that its deficiency has similar sleep-suppressing effects.
“Our findings suggest that there is a signaling pathway within brain cells from LKB1 to SIK3 and then to HDAC4,” says Professor Masashi Yanagisawa, co-senior author of the study.
“This pathway leads to phosphorylation of HDAC4, which promotes sleep, probably because it affects the expression of sleep-promoting genes.”