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| Item Type: | Article |
|---|---|
| Title: | Sequential changes in calcium transients during M phase regulate cardiomyocyte proliferation |
| Creators: |
Liu, Honghai  ORCID: https://orcid.org/0000-0002-0693-6083, Ammanamanchi, Niyatie ORCID: https://orcid.org/0000-0002-9335-3512, Mich-Basso, Jocelyn D. ORCID: https://orcid.org/0009-0003-1316-6851, Panama, Brian K. ORCID: https://orcid.org/0009-0004-9627-2576, Li, Yao ORCID: https://orcid.org/0000-0002-7872-1495, Huang, Winston ORCID: https://orcid.org/0009-0009-6289-3928, Almeida, Dena ORCID: https://orcid.org/0000-0002-7286-2027, Lewarchik, Christopher M., Lo, Brendan ORCID: https://orcid.org/0009-0006-8766-1881, Wu, Yijen ORCID: https://orcid.org/0000-0001-9509-5417, Gotthardt, Michael ORCID: https://orcid.org/0000-0003-1788-3172, Kotlikoff, Michael I. ORCID: https://orcid.org/0000-0001-9879-1899, Baehr, Wolfgang ORCID: https://orcid.org/0000-0001-5003-9550, Rasmusson, Randall ORCID: https://orcid.org/0009-0005-6641-7209, Salama, Guy ORCID: https://orcid.org/0000-0002-5306-8178 and Kühn, Bernhard ORCID: https://orcid.org/0000-0002-1855-7072
|
| Abstract: | Heart muscle growth and regeneration require the proliferation of cardiomyocytes. Rapid pulsatile increases in cytosolic Ca(2+) concentration, called calcium transients (CaTs), trigger cardiomyocyte contractions, but how cardiomyocytes adapt Ca(2+) signaling during proliferation is largely unknown. Here, we show that cardiomyocyte proliferation requires changes in Ca(2+) signaling. Cardiomyocytes undergo a sequence of CaT changes during M phase: CaT amplitudes begin to decline in prometaphase, reach a minimum in metaphase, rise during anaphase, and return to the original state in daughter cardiomyocytes. Spindle poles show decreased Ca(2+) levels during prometaphase and metaphase. Localized reduction of Ca(2+) levels at spindle poles is mediated by dynein 1-dependent SERCA2a accumulation. Active cyclin-dependent kinase 1 (CDK1) induces both the decrease in CaT amplitudes and the accumulation of SERCA2a at the spindle poles, whereas CDK1 inhibition reverses these effects. Forcing an increase in cytosolic Ca(2+) levels by blocking SERCA2a during prometaphase and metaphase disrupts mitosis and produces binucleated cardiomyocytes, underscoring the essential role of Ca(2+) signaling changes for cardiomyocyte proliferation. |
| Keywords: | CDC2 Protein Kinase, Calcium, Calcium Signaling, Cardiac Myocytes, Cell Division, Cell Proliferation, Cultured Cells, Dyneins, Mitosis, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Spindle Apparatus, Animals, Mice |
| Source: | Journal of Cell Biology |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Volume: | 225 |
| Number: | 8 |
| Page Range: | e202505134 |
| Date: | 3 August 2026 |
| Official Publication: | https://doi.org/10.1083/jcb.202505134 |
| PubMed: | View item in PubMed |
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