Na+/Ca2+ exchanger mediates cold Ca2+ signaling conserved for temperature-compensated circadian rhythms

Naohiro Kon, Hsin Tzu Wang, Yoshiaki S. Kato, Kyouhei Uemoto, Naohiro Kawamoto, Koji Kawasaki, Ryosuke Enoki, Gen Kurosawa, Tatsuto Nakane, Yasunori Sugiyama, Hideaki Tagashira, Motomu Endo, Hideo Iwasaki, Takahiro Iwamoto*, Kazuhiko Kume, Yoshitaka Fukada

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Circadian rhythms are based on biochemical oscillations generated by clock genes/proteins, which independently evolved in animals, fungi, plants, and cyanobacteria. Temperature compensation of the oscillation speed is a common feature of the circadian clocks, but the evolutionary-conserved mechanism has been unclear. Here, we show that Na+/Ca2+ exchanger (NCX) mediates cold-responsive Ca2+ signaling important for the temperature-compensated oscillation in mammalian cells. In response to temperature decrease, NCX elevates intracellular Ca2+, which activates Ca2+/calmodulin-dependent protein kinase II and accelerates transcriptional oscillations of clock genes. The cold-responsive Ca2+ signaling is conserved among mice, Drosophila, and Arabidopsis. The mammalian cellular rhythms and Drosophila behavioral rhythms were severely attenuated by NCX inhibition, indicating essential roles of NCX in both temperature compensation and autonomous oscillation. NCX also contributes to the temperature-compensated transcriptional rhythms in cyanobacterial clock. Our results suggest that NCX-mediated Ca2+ signaling is a common mechanism underlying temperature-compensated circadian rhythms both in eukaryotes and prokaryotes.

Original languageEnglish
Article numbereabe8132
JournalScience Advances
Issue number18
Publication statusPublished - 2021 Apr

ASJC Scopus subject areas

  • General


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