A light-induced small G-protein gem limits the circadian clock phase-shift magnitude by inhibiting voltage-dependent calcium channels

Matsuo, Masahiro; Seo, Kazuyuki; Taruno, Akiyuki; Mizoro, Yasutaka; Yamaguchi, Yoshiaki; Doi, Masao; Nakao, Rhyuta; Kori, Hiroshi; Abe, Takaya; Ohmori, Harunori; Tominaga, Keiko; Okamura, Hitoshi

doi:10.1016/j.celrep.2022.110844

Cited by 14 publications

(16 citation statements)

References 52 publications

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“…This indicates that the light signaling mechanism for cFos induction is different from the one mediating induction of Per1 and Dec1. Interestingly, however, the light-inducible genes Sik1 and Gem, which are involved in limiting the effects of light on the clock 68,69 were not light-inducible in shCdk5 animals (Fig. 6i, j) supporting the view that the factors that drive (Per1, Dec1) or limit (Sik1, Gem) the effects of light on the clock are regulated by the same mechanism.…”

Section: Discussionmentioning

confidence: 76%

“…6i, j) supporting the view that the factors that drive (Per1, Dec1) or limit (Sik1, Gem) the effects of light on the clock are regulated by the same mechanism. Interestingly, neither lack of Per1, Dec1 20,82 nor Sik1 or Gem 68,69 alone abolish phase delays. Of note is that lack of cFos or Egr1 did not affect phase delays either 83,84 .…”

Section: Discussionmentioning

confidence: 96%

“…The light-inducible small G-protein Gem limits the circadian clock phase-shift magnitude by inhibiting voltage-dependent calcium channels 69 . We tested whether a light pulse affected Gem expression in the SCN and whether this was involving Cdk5.…”

Section: Cdk5 Affects Light-induced Gene Expressionmentioning

confidence: 99%

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Cyclin-dependent kinase 5 (Cdk5) activity is modulated by light and gates rapid phase shifts of the circadian clock

Brenna,

Borsa,

Saro

et al. 2024

Preprint

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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 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 PKA - CaMK - CREB signaling pathway. Our experiments identified an important light modulated kinase that affects rapid clock phase adaptation, which is important to adapt activity onset to seasonal changes, jet-lag and shift work.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 96%

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Cyclin-dependent kinase 5 (Cdk5) activity is modulated by light and gates rapid phase shifts of the circadian clock

Brenna,

Borsa,

Saro

et al. 2024

Preprint

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“…Interestingly among the genes differentially expressed are Dusp4 and Rasd1 both of which are key modulators of the SCN light response through their actions on the critical NMDAR, MAPK/ERK and CREB/CRE light transduction pathway (Cheng et al, 2004;Hamnett et al, 2019) for Dusp4 are described in the neuropeptide signaling genes results. In addition, Gem, which also modulates SCN phase resetting to light through negative feedback onto the MAPK/ERK pathway (Matsuo et al, 2022), was one of the very few genes that showed a significant phase delay in Long compared to Short (Fig. 6B) (Carlson et al, 2016).…”

Section: Light Responsive Genesmentioning

confidence: 99%

Gene expression plasticity of the mammalian brain circadian clock in response to photoperiod

Cox,

Gianonni-Guzmán,

Cartailler

et al. 2024

Preprint

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Seasonal daylength, or circadian photoperiod, is a pervasive environmental signal that profoundly influences physiology and behavior. In mammals, the central circadian clock resides in the suprachiasmatic nuclei (SCN) of the hypothalamus and synchronizes, or entrains, physiology and behavior to the prevailing light cycle from retinal input. The process of entrainment induces considerable plasticity in the SCN, but the molecular mechanisms underlying SCN plasticity are incompletely understood. Entrainment to different photoperiods persistently alters the phase, waveform, period, and resetting properties of the SCN and its driven rhythms. To elucidate novel molecular mechanisms of photoperiod plasticity, we performed RNAseq on whole SCN dissected from mice raised in Long (LD 16:8) and Short (LD 8:16) photoperiods. Using differential rhythms analysis, we showed that fewer rhythmic genes were detected in Long photoperiod and that there was an overall phase advance of gene expression rhythms of 4-6 hours. However, a few genes showed significant phase delays, including GTP binding protein overexpressed in skeletal muscle (Gem), an SCN light responsive gene and light response modulator. Using differential expression analysis, we found significant expression changes in the clock-associated gene timeless circadian clock 1 (Timeless) and abundant changes in expression levels of SCN neural signaling genes related to light responses, neuropeptides, GABA, ion channels, and serotonin. Particularly striking were differences across photoperiods in the expression of the SCN neuropeptide signaling genes, prokineticin receptor 2 (Prokr2) and cholecystokinin (Cck), as well as convergent regulation of the expression of three SCN light response genes, dual specificity phosphatase 4 (Dusp4) and RAS, dexamethasone-induced 1 (Rasd1), andGem. Transcriptional modulation ofDusp4andRasd1,and phase regulation ofGem,are compelling candidate molecular mechanisms for photoperiod-induced plasticity in the SCN light response. Similarly, transcriptional modulation ofProkr2andCckmay critically support SCN neural network reconfiguration during photoperiodic entrainment. Our findings identify the SCN light response and neuropeptide signaling gene sets as rich substrates for elucidating novel mechanisms of photoperiod plasticity.

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“…Since the SCN is the key site governing all circadian physiology of the body, we have been progressing to identify key SCN signaling molecules that are specific for circadian generation and synchronization (Okamura, 2007). Through this project, we identified the circadian roles of Rgs16 (Doi et al, 2011), vasopressin (Yamaguchi et al, 2013), and Gem (Matsuo et al, 2022). In the present study, we focused on the substances expressed in SCN astrocytes.…”

mentioning

confidence: 99%

Prolonged Light Exposure Induces Circadian Impairment in Aquaporin-4-Knockout Mice

et al. 2023

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Astrocytes are densely present in the suprachiasmatic nucleus (SCN), which is the master circadian oscillator in mammals, and are presumed to play a key role in circadian oscillation. However, specific astrocytic molecules that regulate the circadian clock are not yet well understood. In our study, we found that the water channel aquaporin-4 (AQP4) was abundantly expressed in SCN astrocytes, and we further examined its circadian role using AQP4-knockout mice. There was no prominent difference in circadian behavioral rhythms between Aqp4-/- and Aqp4+/+ mice subjected to light-dark cycles and constant dark conditions. However, exposure to constant light induced a greater decrease in the Aqp4-/- mice rhythmicity. Although the damped rhythm in long-term constant light recovered after transfer to constant dark conditions in both genotypes, the period until the reappearance of original rhythmicity was severely prolonged in Aqp4-/- mice. In conclusion, AQP4 absence exacerbates the prolonged light-induced impairment of circadian oscillations and delays their recovery to normal rhythmicity.

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A light-induced small G-protein gem limits the circadian clock phase-shift magnitude by inhibiting voltage-dependent calcium channels

Cited by 14 publications

References 52 publications

Cyclin-dependent kinase 5 (Cdk5) activity is modulated by light and gates rapid phase shifts of the circadian clock

Cyclin-dependent kinase 5 (Cdk5) activity is modulated by light and gates rapid phase shifts of the circadian clock

Gene expression plasticity of the mammalian brain circadian clock in response to photoperiod

Prolonged Light Exposure Induces Circadian Impairment in Aquaporin-4-Knockout Mice

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