Calcium signaling to nucleus via store-operated system during cell cycle in retinal neuroepithelium

Abstract

Intracellular Ca 2+ is a regulatory signal for cell proliferation. To reveal Ca 2+ signal dynamics during cell cycle, we applied Ca 2+ fluorescence imaging to the neural retina of chick embryo, where the soma changes its position during the cell cycle. Purinoceptors were stimulated to cause Ca 2+ release from Ca 2+ stores, since the purinoceptor activation promotes DNA synthesis. Ca 2+ rises occurred in the nucleoplasm of cells at around S-phase. The soma of S-phase cell is located in the inner layer of the retinal neuroepithelium and issues an outer process, which extends to the ventricular surface. Fluorescent probes for endoplasmic reticulum (ER) showed that the ERs in the outer process and the nuclear envelope (NE) or peri-nuclear ER formed the Ca 2+ store. Depletion of the Ca 2+ store induced capacitative Ca 2+ entry (CCE), which caused Ca 2+ rises in the terminal of outer process and soma. The store-operated Ca 2+ signaling declined in M-phase cells and postmitotic cells (retinal ganglion cells (RGCs)) with the loss of the outer process. These results suggest that the Ca 2+ signaling to nucleus via the store-operated system including the ERs in the outer process is crucial for the cell cycle progression in the retinal neuroepithelium.