title: Mitogen- and stress-activated protein kinase 1 modulates photic entrainment of the suprachiasmatic circadian clock.
abstract: The master circadian clock in mammals, the suprachiasmatic nucleus (SCN), is under the entraining influence of the external light cycle. At a mechanistic level, intracellular signaling via the p42/44 mitogen-activated protein kinase pathway appears to play a central role in light-evoked clock entrainment; however, the precise downstream mechanisms by which this pathway influences clock timing are not known. Within this context, we have previously reported that light stimulates activation of the mitogen-activated protein kinase effector mitogen-stress-activated kinase 1 (MSK1) in the SCN. In this study, we utilised MSK1(-/-) mice to further investigate the potential role of MSK1 in circadian clock timing and entrainment. Locomotor activity analysis revealed that MSK1 null mice entrained to a 12 h light/dark cycle and exhibited circadian free-running rhythms in constant darkness. Interestingly, the free-running period in MSK1 null mice was significantly longer than in wild-type control animals, and MSK1 null mice exhibited a significantly greater variance in activity onset. Further, MSK1 null mice exhibited a significant reduction in the phase-delaying response to an early night light pulse (100 lux, 15 min), and, using an 8 h phase-advancing 'jet-lag' experimental paradigm, MSK1 knockout animals exhibited a significantly delayed rate of re-entrainment. At the molecular level, early night light-evoked cAMP response element-binding protein (CREB) phosphorylation, histone phosphorylation and Period1 gene expression were markedly attenuated in MSK1(-/-) animals relative to wild-type mice. Together, these data provide key new insights into the molecular mechanisms by which MSK1 affects the SCN clock.
authors.affiliation: Department of Neuroscience, Ohio State University, Columbus, OH, USA.
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Cao
authors.forename: Greg Q
authors.initials: GQ
authors.lastname: Butcher
authors.forename: Kate
authors.initials: K
authors.lastname: Karelina
authors.forename: J Simon
authors.initials: JS
authors.lastname: Arthur
authors.forename: Karl
authors.initials: K
authors.lastname: Obrietan
mesh_terms: D000818:Animals; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D020179:Jet Lag Syndrome; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010775:Photic Stimulation; D017440:Photoperiod; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics*; D013493:Suprachiasmatic Nucleus / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D006657:Histones; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1