A centrosome calcium signal is essential for mammalian cell mitosis

Abstract

AbstractTo 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 (Ca2+) could influence mitosis. Here we explore this key question in the cell biology of mammalian cells by targeting high affinity genetically encoded Ca2+ sensors to mitosis specific subcellular locations. We reveal a prolonged yet spatially restricted Ca2+ signal at the centrosomes of mitotic cells using an actin-targeted Ca2+ sensor. Local depletion of Ca2+ at centrosomes using flash-photolysis of the caged Ca2+ chelator diazo-2 arrests mitosis and we provide evidence that this signal emanates from the endoplasmic reticulum. In summary, we characterize a centrosomal Ca2+ signal as a functionally essential input into mitosis. This extends our understanding of the complex regulatory network controlling cell division and pinpoints Ca2+ as an important controller of this fundamental process.