NDLI: Regulation of MAPK/ERK signaling and photic entrainment of the suprachiasmatic nucleus circadian clock by Raf kinase inhibitor protein.

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Regulation of MAPK/ERK signaling and photic entrainment of the suprachiasmatic nucleus circadian clock by Raf kinase inhibitor protein.

Content Provider	Semantic Scholar
Author	Antoun, Ghadi Bouchard-Cannon, Pascale Cheng, Hai-Ying Mary
Copyright Year	2012
Abstract	Activation of the MAPK/ERK signaling cascade in the suprachiasmatic nucleus (SCN) is a key event that couples light to circadian clock entrainment. However, we do not fully understand the mechanisms that shape the properties of MAPK/ERK signaling in the SCN, and how these mechanisms may influence overt circadian rhythms. Here we show that Raf kinase inhibitor protein (RKIP) controls the kinetics of light-induced MAPK/ERK activity in the SCN and photic entrainment of behavioral rhythms. Light triggers robust phosphorylation of RKIP in the murine SCN and dissociation of RKIP and c-Raf. Overexpression of a nonphosphorylatable form of RKIP in the SCN of transgenic mice blocks light-induced ERK1/2 activation in the SCN and severely dampens light-induced phase delays in behavioral rhythms. Conversely, in RKIP knock-out (RKIP(-/-)) mice, light-induced ERK1/2 activity in the SCN is prolonged in the early and late subjective night, resulting in augmentation of the phase-delaying and -advancing effects of light. Reentrainment to an advancing light cycle was also accelerated in RKIP(-/-) mice. In relation to the molecular clockwork, genetic deletion of RKIP potentiated light-evoked PER1 and PER2 protein expression in the SCN in the early night. Additionally, RKIP(-/-) mice displayed enhanced transcriptional activation of mPeriod1 and the immediate early gene c-Fos in the SCN in response to a phase-delaying light pulse. Collectively, our data reveal an important role of RKIP in the regulation of MAPK/ERK signaling in the SCN and photic entrainment of the SCN clock.
File Format	PDF HTM / HTML
DOI	10.1523/JNEUROSCI.5650-11.2012
PubMed reference number	22492043
Journal	Medline
Volume Number	32
Issue Number	14
Alternate Webpage(s)	http://www.jneurosci.org/content/jneuro/32/29/10101.full.pdf
Alternate Webpage(s)	http://www.jneurosci.org/content/jneuro/32/14/4867.full.pdf
Journal	The Journal of neuroscience : the official journal of the Society for Neuroscience
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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