Cell cycle-dependent regulation of store-operated ICRAC and Mg2+-nucleotide-regulated MagNuM (TRPM7) currents

Calcium signaling is a central mechanism for numerous cellular functions and particularly relevant for immune cell proliferation. However, the role of calcium influx in mitotic cell cycle progression is largely unknown. We here report that proliferating rat mast cells RBL-2H3 tightly control their major store-operated calcium influx pathway, ICRAC, during cell cycle progression. While ICRAC is maintained at control levels during the first gap phase (G1), the current is significantly up-regulated in preparation for and during chromatin duplication. However, mitosis strongly suppresses ICRAC. Non-proliferating cells deprived of growth hormones strongly down-regulate ICRAC while increasing cell volume. We further show that the other known calcium (and magnesium) influx pathway in mast cells, the TRPM7-like magnesium-nucleotide-regulated metal (MagNuM) current, is largely uncoupled from cell cycle regulation except in G1. Taken together, our results demonstrate that both store-operated calcium influx via ICRAC and MagNuM are regulated at crucial checkpoints during cell cycle progression.