Cyclin-dependent kinase 5 (Cdk5) activity is modulated by light and gates rapid phase shifts of the circadian clock
DOKPE
- Brenna, Andrea Department of Biology, Department of Medicine, University of Fribourg, Switzerland
- Zhihong, Yang Department of Medicine, University of Fribourg, Switzerland
- Saro, Gabriella Department of Biology, University of Fribourg, Switzerland
- Ripperger, Jürgen A. Department of Biology, University of Fribourg, Switzerland
- Glauser, Dominique A. Department of Biology, University of Fribourg, Switzerland
- Albrecht, Urs Department of Biology, University of Fribourg, Switzerland
- 2024
Published in:
- bioRxiv. - Cold Spring Harbor Laboratory. - 2024
English
The circadian clock allows organisms to coordinate biochemical and physiological processes
over one day. Changes in lighting conditions as they occur naturally over seasons or
manmade by jet lag or shift work, advance or delay clock phase to synchronize physiology to
the environment. Within the suprachiasmatic nucleus (SCN) of the hypothalamus, circadian
timekeeping and resetting have been shown to depend on both membrane depolarization and
intracellular second-messenger signaling. In both processes, voltage-gated calcium channels
(VGCCs) mediate calcium influx resulting in the activation of intracellular signaling
pathways that activate Period (Per) gene expression. However, the precise mechanism how
these processes are gated in a concerted manner is unknown. Here we show that cyclingdependent kinase 5 (Cdk5) activity is modulated by light and gates phase shifts of the
circadian clock. We found that knock-down of Cdk5 in the SCN of mice affects phase delays
but not phase advances. This is associated with uncontrolled calcium influx into SCN neurons
and an unregulated protein kinase A (PKA) – calcium calmodulin dependent kinase (CaMK)
– cAMP response element-binding protein (CREB) signaling pathway. Accordingly, genes
such as Per1 are not induced by light in the SCN of Cdk5 knock-down mice. Our
experiments identified an important light modulated kinase that affects rapid clock phase
adaptation. This finding indicates how light responsiveness and clock phase are coordinated
to adapt activity onset to seasonal changes, jet-lag and shift work.
over one day. Changes in lighting conditions as they occur naturally over seasons or
manmade by jet lag or shift work, advance or delay clock phase to synchronize physiology to
the environment. Within the suprachiasmatic nucleus (SCN) of the hypothalamus, circadian
timekeeping and resetting have been shown to depend on both membrane depolarization and
intracellular second-messenger signaling. In both processes, voltage-gated calcium channels
(VGCCs) mediate calcium influx resulting in the activation of intracellular signaling
pathways that activate Period (Per) gene expression. However, the precise mechanism how
these processes are gated in a concerted manner is unknown. Here we show that cyclingdependent kinase 5 (Cdk5) activity is modulated by light and gates phase shifts of the
circadian clock. We found that knock-down of Cdk5 in the SCN of mice affects phase delays
but not phase advances. This is associated with uncontrolled calcium influx into SCN neurons
and an unregulated protein kinase A (PKA) – calcium calmodulin dependent kinase (CaMK)
– cAMP response element-binding protein (CREB) signaling pathway. Accordingly, genes
such as Per1 are not induced by light in the SCN of Cdk5 knock-down mice. Our
experiments identified an important light modulated kinase that affects rapid clock phase
adaptation. This finding indicates how light responsiveness and clock phase are coordinated
to adapt activity onset to seasonal changes, jet-lag and shift work.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Biologie, Département de Médecine
- Language
-
- English
- License
- License undefined
- Open access status
- green
- Identifiers
- Persistent URL
- https://folia.unifr.ch/unifr/documents/328667
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