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

Abstract

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, I CRAC , during cell cycle progression. While I CRAC is maintained at control levels during the first gap phase (G1), the current is significantly upregulated in preparation for and during chromatin duplication. However, mitosis strongly suppresses I CRAC . Non-proliferating cells deprived of growth hormones strongly down-regulate I CRAC 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 I CRAC and MagNuM are regulated at crucial checkpoints during cell cycle progression.

Orai1 internalization and STIM1 clustering inhibition modulate SOCE inactivation during meiosis

“…SOCE is inhibited as the oocyte commits to meiosis (12), and MPF activation is sufficient for SOCE inactivation (12). As is the case in Xenopus eggs, SOCE inactivates during mitosis of mammalian cells (13,18). Here we show that SOCE inactivation during meiosis is the result of Orai1 internalization and to the inability of STIM1 to cluster in response to store depletion.…”

Ca2+ signaling differentiation during oocyte maturation

“…Furthermore, as is the case in Xenopus eggs, SOCE inactivates during mitosis of mammalian cells (Preston et al, 1991;Tani et al, 2007), arguing that MPF activation typically leads to SOCE inactivation, since mitosis also requires MPF/cdk1. Therefore, mammalian eggs are the exception in terms of maintaining SOCE functional during the division phase of the cell cycle.…”

Microtubule remodeling mediates the inhibition of store-operated calcium entry (SOCE) during mitosis in COS-7 cells

“…We recently observed that, unlike interphase cells, the depletion of intracellular calcium stores with ATP was not followed by SOCE in mitotic cells which indicates the inhibition of this vital [Ca 2+ ]i -regulating mechanism. A few reports have implied either a down-regulation or a complete absence of SOCE in mitotic cells presumably due to uncoupling between cell surface channels and the ER (Volpi and Berlin, 1988;Preston et al, 1991;Tani et al, 2007). However, no attempts have been made to substantiate these findings and possibly shed some light on the cellular mechanisms involved.…”