New route to Aβ

ER for tiny calcium domains iny microdomains of mitosis-driving calcium signals are created by the ER, as shown by Parry et al. on page 47. Although these calcium spikes were suspected to exist—based on findings that blocking calcium signals prevents mitosis in sea urchins—they have often eluded visualization. Parry et al. were able to detect the calcium spikes by using fly embryos, in which the space between the ER and the mitotic spindle is wider than in other systems. The group identified two sets of mitotic calcium signals that were shaped by the ER—one large spike between the embryo cortex and the ER, and two smaller spikes between the ER and the spindle. Cortical calcium spiked during interphase. At the cortex, calcium might be inducing the actin rearrangements that separate the nuclei of early fly embryos, as recent findings showed that calcium spikes are needed for cytokinesis. The two spindle-adjacent spikes occurred just before mitosis and at anaphase. These spikes probably activate calmodulin and its kinase, but their downstream targets are not yet known. As inhibitors of calcium release prevented anaphase chromatin separation, securin and separase are possible targets. Higher concentrations of inhibitors even prevented nuclear envelope breakdown. The authors suspect that cyclins and Cdks are other downstream targets, as well as possible initiators, of the calcium signals. T Nuclear calcium spikes (green) at prophase (left) and metaphase (right) are surrounded by ER (red).