記述言語：英語   掲載種別：研究論文（学術雑誌）  

Circadian rhythms are a universal property of organisms, and a defining property of these oscillators is the ability to maintain a precise period at different temperatures. Indeed, the discovery in the 1950s of this property, known as "temperature compensation," was a watershed event in our understanding of biological timekeeping. Since that time, however, almost no general principles have emerged that uncover the mechanistic basis of how circadian timekeepers defy the "rules" of temperature dependence of biochemical reactions. A genetic investigation of circadian temperature compensation reveals that the sensing of metabolism and ensuing modulation of the core mechanism preserves a constant circadian period. Intracellular redox sensing of metabolic rate is intrinsic to this compensation, and this relationship is conserved in bacterial and mammalian cells. These insights explain previously inexplicable observations of the interaction between redox reactions and circadian timekeeping. These results introduce a previously unknown linkage between temperature compensation and metabolism.

DOI： 10.1038/s41467-026-77031-z

PubMed

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）  

DOI： 10.1073/pnas.2509943123

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掲載種別：研究論文（学術雑誌）   出版者・発行元：American Physical Society (APS)  

Notch signaling is a ubiquitous and versatile intercellular signaling system that drives collective behaviors and pattern formation in biological tissues. During embryonic development, Notch is involved in generation of collective biochemical oscillations that form the vertebrate body segments, and its failure results in embryonic defects. Notch ligands of the Delta family are key components of this collective rhythm, but it is unclear how different Delta ligands with distinct properties contribute to relaying information among cells. Motivated by the zebrafish segmentation clock, in this work we propose a theory describing interactions between biochemical oscillators, where Notch receptor is bound by both oscillatory and nonoscillatory Delta ligands. Based on previous in vitro binding studies, we first consider Notch activation by Delta dimers. This hypothesis is consistent with experimental observations in conditions of perturbed Notch signaling. Then we test an alternative hypothesis where Delta monomers directly bind and activate Notch, and show that this second model can also describe the experimental observations. We show that these two hypotheses assign different roles for a non-oscillatory ligand, as a binding partner or as a baseline signal. Finally, we discuss experiments to distinguish between the two scenarios. Broadly, this work highlights how a multiplicity of ligands may be harnessed by a signaling system to generate versatile responses.

DOI： 10.1103/7g6x-b238

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その他リンク： http://harvest.aps.org/v2/journals/articles/10.1103/7g6x-b238/fulltext

担当区分：筆頭著者,　責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Cold Spring Harbor Laboratory  

DOI： 10.1103/PhysRevE.111.024407

Scopus

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