The slow-acting G-protein Gz defines the duration of circadian rest time

Tanaka, Y.; Fujita, Y.; Macpherson, T.; Harui, A.; Kunisue, S.; Setsu, G.; Shao, X.; Ono, D.; Hikida, T.; Matsuda, M.; Okamura, H.; Hasegawa, E.; Doi, M.

doi:10.64898/2026.05.23.727383

bioRxiv · 10.64898/2026.05.23.727383

The slow-acting G-protein Gz defines the duration of circadian rest time

Tanaka, Y.·Fujita, Y.·Macpherson, T.·Harui, A.·Kunisue, S.·Setsu, G.·Shao, X.·Ono, D.·Hikida, T.·Matsuda, M.·Okamura, H.·Hasegawa, E.·Doi, M.

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Abstract

Duration of nightly rest is a trait that varies between individuals, influenced by a complex interplay between multiple genetic and environmental factors. The central circadian clock that orchestrates daily rhythm in behavior/sleep resides in the suprachiasmatic nucleus (SCN). Yet, how the SCN encodes the "length" of the circadian rest phase ({rho}) remains an open question. Here we demonstrate that the unique G-protein-subtype Gz contributes to this process by sculpting the waveform of the circadian cAMP-PKA activity rhythm within the SCN. Genetic deletion and subsequent rescue of Gz expression reversibly altered the {rho} duration, shifting it from [~]10 h in Gz+/+ mice to [~]7.5 h in Gz-/-; mice, accompanied by proportional changes in peak cAMP-PKA activity duration and transcriptome remodeling in the SCN. Notably, intra-SCN cAMP activation led to behavioral rest, with Gz specifically shaping this response without affecting 24-h rhythmicity. These findings suggest that the SCN is not merely a rhythm-generator, but actively allocates the {rho}-rest period via Gz signaling.

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Tanaka, Y., Fujita, Y., Macpherson, T., Harui, A., Kunisue, S., Setsu, G., Shao, X., Ono, D., Hikida, T., Matsuda, M., Okamura, H., Hasegawa, E., Doi, M.. 2026-05-27. The slow-acting G-protein Gz defines the duration of circadian rest time. https://doi.org/10.64898/2026.05.23.727383

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