Cell cycle-dependent regulation of store-operated I(CRAC) 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, I(CRAC), during cell cycle progression. While I(CRAC) 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 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.
Tani
Dawn
D
Laboratory of Cell and Molecular Signaling, Center for Biomedical Research at The Queen's Medical Center and John A. Burns School of Medicine at the University of Hawaii, 1301 Punchbowl Street, UHT 8, Honolulu, HI 96813, USA.
Monteilh-Zoller
Mahealani K
MK
Fleig
Andrea
A
Penner
Reinhold
R
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism*; D051381:Rats; D050053:TRPM Cation Channels / Q000378:metabolism*
D015220:Calcium Channels; D036341:Intercellular Signaling Peptides and Proteins; D050053:TRPM Cation Channels; C486584:Trpm7 protein, rat; D008274:Magnesium