Photic regulation of the mTOR signaling pathway in the suprachiasmatic circadian clock.
Here we analyzed the light-responsiveness of the mammalian target of rapamycin (mTOR) cascade, a key regulator of inducible translation, in the suprachiasmatic nuclei (SCN), the locus of the master circadian clock. Brief light exposure during the subjective night, but not during the subjective day, triggered rapid phosphorylation (a marker of catalytic activity) of the mTOR translation effectors p70 S6K, ribosomal S6 protein (S6) and 4E-BP1. In the absence of photic stimulation, marked S6 and 4E-BP1 phosphorylation was detected, indicating tonic mTOR activity in the SCN. Light stimulated the colocalized activation of p70 S6K and extracellular signal-regulated protein kinase (ERK), and pharmacological disruption of ERK signaling abolished light-induced mTOR activity, revealing that the MAPK cascade is an essential intermediate that couples light to mTOR. Together these data identify a light-responsive mTOR cascade in the SCN, and thus, raise the possibility that inducible translation contributes to the clock entrainment process.
Cao
Ruifeng
R
Department of Neuroscience, Ohio State University, Columbus, OH 43210, USA.
Lee
Boyoung
B
Cho
Hee-Yeon
HY
Saklayen
Sanjida
S
Obrietan
Karl
K
D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D000242:Cyclic AMP; D017362:Cyclic AMP Response Element-Binding Protein; D003623:Dark Adaptation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010775:Photic Stimulation / Q000379:methods*; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000737:chemistry / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
D017362:Cyclic AMP Response Element-Binding Protein; D000242:Cyclic AMP; D011494:Protein Kinases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases