RRC ID 67776
Author Park M, Miyoshi C, Fujiyama T, Kakizaki M, Ikkyu A, Honda T, Choi J, Asano F, Mizuno S, Takahashi S, Yanagisawa M, Funato H.
Title Loss of the conserved PKA sites of SIK1 and SIK2 increases sleep need.
Journal Sci Rep
Abstract Although sleep is one of the most conserved behaviors, the intracellular mechanism regulating sleep/wakefulness remains unknown. We recently identified a protein kinase, SIK3, as a sleep-regulating molecule. Mice that lack a well-conserved protein kinase A (PKA) phosphorylation site, S551, showed longer non-rapid eye movement (NREM) sleep and increased NREMS delta density. S551 of SIK3 is conserved in other members of the SIK family, such as SIK1 (S577) and SIK2 (S587). Here, we examined whether the PKA phosphorylation sites of SIK1 and SIK2 are involved in sleep regulation by generating Sik1S577A and Sik2S587A mice. The homozygous Sik1S577A mice showed a shorter wake time, longer NREMS time, and higher NREMS delta density than the wild-type mice. The heterozygous and homozygous Sik2S587A mice showed increased NREMS delta density. Both the Sik1S577A and Sik2S587A mice exhibited proper homeostatic regulation of sleep need after sleep deprivation. Despite abundant expression of Sik1 in the suprachiasmatic nucleus, the Sik1S577A mice showed normal circadian behavior. Although Sik2 is highly expressed in brown adipose tissue, the male and female Sik2S587A mice that were fed either a chow or high-fat diet showed similar weight gain as the wild-type littermates. These results suggest that PKA-SIK signaling is involved in the regulation of sleep need.
Volume 10(1)
Pages 8676
Published 2020-5-26
DOI 10.1038/s41598-020-65647-0
PII 10.1038/s41598-020-65647-0
PMID 32457359
PMC PMC7250853
MeSH Adipose Tissue, Brown / metabolism Amino Acid Substitution / genetics Animals Body Weight / genetics Brain Waves / genetics Cell Line Circadian Rhythm / genetics Cyclic AMP-Dependent Protein Kinases / metabolism* Female HEK293 Cells Humans Male Mice Mice, Inbred C57BL Mice, Knockout Phosphorylation Protein Serine-Threonine Kinases / genetics* Protein Serine-Threonine Kinases / metabolism Signal Transduction / physiology Sleep, Slow-Wave / genetics* Sleep, Slow-Wave / physiology Wakefulness / genetics* Wakefulness / physiology
IF 3.998
DNA material pCDNA-FLAG-mSIK1 (RDB19160) pCDNA-FLAG-mSIK1(S577A) (RDB19161) pCDNA-FLAG-mSIK2 (RDB19162) pCDNA-FLAG-mSIK2(S587A) (RDB19163) pCDNA-FLAG-mSIK3 (RDB19164) pCDNA-FLAG-mSIK3(S551A) (RDB19165)
Human and Animal Cells 293T(RCB2202)