A light-induced small G-protein gem limits the circadian clock phase-shift magnitude by inhibiting voltage-dependent calcium channels
| Autor: | Masahiro Matsuo, Kazuyuki Seo, Akiyuki Taruno, Yasutaka Mizoro, Yoshiaki Yamaguchi, Masao Doi, Rhyuta Nakao, Hiroshi Kori, Takaya Abe, Harunori Ohmori, Keiko Tominaga, Hitoshi Okamura |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Gem
light-induced endocrine system diseases Calcium Channels L-Type RGK small G-protein voltage-dependent calcium channels General Biochemistry Genetics and Molecular Biology Circadian Rhythm Mice Inbred C57BL Mice phase-shift Circadian Clocks circadian clock Animals Suprachiasmatic Nucleus Monomeric GTP-Binding Proteins |
| Zdroj: | Cell Reports. 39:110844 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2022.110844 |
| Popis: | Calcium signaling is pivotal to the circadian clockwork in the suprachiasmatic nucleus (SCN), particularly in rhythm entrainment to environmental light-dark cycles. Here, we show that a small G-protein Gem, an endogenous inhibitor of high-voltage-activated voltage-dependent calcium channels (VDCCs), is rapidly induced by light in SCN neurons via the calcium (Ca²⁺)-mediated CREB/CRE transcriptional pathway. Gem attenuates light-induced calcium signaling through its interaction with VDCCs. The phase-shift magnitude of locomotor activity rhythms by light, at night, increases in Gem-deficient (Gem⁻/⁻) mice. Similarly, in SCN slices from Gem⁻/⁻ mice, depolarizing stimuli induce larger phase shifts of clock gene transcription rhythms that are normalized by the application of an L-type VDCC blocker, nifedipine. Voltage-clamp recordings from SCN neurons reveal that Ca²⁺ currents through L-type channels increase in Gem⁻/⁻ mice. Our findings suggest that transcriptionally activated Gem feeds back to suppress excessive light-evoked L-type VDCC activation, adjusting the light-induced phase-shift magnitude to an appropriate level in mammals. 光誘導物質による新しい体内時計の同調制御機構 --光により誘導される神経細胞の活動抑制物質の発見--. 京都大学プレスリリース. 2022-05-26. |
| Databáze: | OpenAIRE |
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