Mitosis defects can lead to premature ageing and cancer. Understanding mitosis regulation therefore has important implications for human disease. Early data suggested that calcium (Ca2+) signals could influence mitosis, but these have hitherto not been observed in mammalian cells. Here, we reveal a prolonged yet spatially restricted Ca2+ signal at the centrosomes of actively dividing cells. Local buffering of the centrosomal Ca2+ signals, by flash photolysis of the caged Ca2+ chelator diazo-2-acetoxymethyl ester, arrests mitosis. We also provide evidence that this Ca2+ signal emanates from the endoplasmic reticulum. In summary, we characterize a unique centrosomal Ca2+ signal as a functionally essential input into mitosis.—Helassa, N., Nugues, C., Rajamanoharan, D., Burgoyne, R. D., Haynes, L. P. A centrosome-localized calcium signal is essential for mammalian cell mitosis.

Mitosis, the accurate segregation of duplicated genetic material into what will become two new daughter cells, is accompanied by extensive membrane remodelling and membrane trafficking activities. Early in mitosis, adherent cells partially detach from the substratum, round up and their surface area decreases. This likely results from an endocytic uptake of plasma membrane material. As cells enter cytokinesis they re-adhere, flatten and exhibit an associated increase in surface area. The identity of the membrane donor for this phase of mitosis remains unclear. Here we show by biochemical and imaging approaches that lysosomes undergo exocytosis during mitosis and that this requires the activity of phosphatidylinositol 4-kinase-III. Inhibition of lysosome exocytosis leads to mitotic failure in a significant proportion of cells suggesting that this facet of lysosome physiology is essential and represents a new regulatory mechanism in mitosis.

The transformation of a single fertilised egg into an adult human consisting of tens of trillions of highly diverse cell types is a marvel of biology. The expansion is largely achieved by cell duplication through the process of mitosis. Mitosis is essential for normal growth, development, and tissue repair and is one of the most tightly regulated biological processes studied. This regulation is designed to ensure accurate segregation of chromosomes into each new daughter cell since errors in this process can lead to genetic imbalances, aneuploidy, that can lead to diseases including cancer. Understanding how mitosis operates and the molecular mechanisms that ensure its fidelity are therefore not only of significant intellectual value but provide unique insights into disease pathology. The purpose of this review is to revisit historical evidence that mitosis can be influenced by the ubiquitous second messenger calcium and to discuss this in the context of new findings revealing exciting new information about its role in cell division.

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.

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