A centrosome calcium signal is essential for mammalian cell mitosis

To generate a complex multicellular organism like a human requires enormous expansion in cell numbers and this is achieved predominantly through mitosis. Defects in mitosis can lead to premature ageing and cancer so understanding how it is regulated has important implications for human disease. Early data from plant and invertebrate model systems indicated that calcium (Ca 2+ ) could influence mitosis. Here we explore this key question in the cell biology of mammalian cells by targeting high affinity genetically encoded Ca 2+ sensors to mitosis specific subcellular locations. We reveal a prolonged yet spatially restricted Ca 2+ signal at the centrosomes of mitotic cells using an actin-targeted Ca 2+ sensor. Local depletion of Ca 2+ at centrosomes using flash-photolysis of the caged Ca 2+ chelator diazo-2 arrests mitosis and we provide evidence that this signal emanates from the endoplasmic reticulum. In summary, we characterize a centrosomal Ca 2+ signal as a functionally essential input into mitosis. This extends our understanding of the complex regulatory network controlling cell division and pinpoints Ca 2+ as an important controller of this fundamental process.