Abstract:
:Environmental cues modulate a variety of intracellular pathways whose signaling is integrated by the molecular mechanism that constitutes the circadian clock. Although the essential gears of the circadian machinery have been elucidated, very little is known about the signaling systems regulating it. Here, we report that signaling mediated by the dopamine D2 receptor (D2R) enhances the transcriptional capacity of the CLOCK:BMAL1 complex. This effect involves the mitogen-activated protein kinase transduction cascade and is associated with a D2R-induced increase in the recruiting and phosphorylation of the transcriptional coactivator cAMP-responsive element-binding protein (CREB) binding protein. Importantly, CLOCK:BMAL1-dependent activation and light-inducibility of mPer1 gene transcription is drastically dampened in retinas of D2R-null mice. Because dopamine is the major catecholamine in the retina, central for the neural adaptation to light, our findings establish a physiological link among photic input, dopamine signaling, and the molecular clock machinery.
journal_name
Proc Natl Acad Sci U S Aauthors
Yujnovsky I,Hirayama J,Doi M,Borrelli E,Sassone-Corsi Pdoi
10.1073/pnas.0510691103subject
Has Abstractpub_date
2006-04-18 00:00:00pages
6386-91issue
16eissn
0027-8424issn
1091-6490pii
0510691103journal_volume
103pub_type
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