Editors' ChoiceCalcium signaling

A Coincidence Detector with a Memory

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Science Signaling  14 Feb 2012:
Vol. 5, Issue 211, pp. ec48
DOI: 10.1126/scisignal.2002954

Calcium signals can trigger changes in gene expression, and one of the major mechanisms for this response is activation of the calcium-dependent phosphatase calcineurin, which dephosphorylates transcription factors of the NFAT (nuclear factor of activated T cells) family, allowing them to translocate into the nucleus. Calcium release–activated calcium (CRAC) channels are plasma membrane channels that open in response to depletion of internal calcium stores and thus contribute to calcium oscillations in cells (see Putney). Kar et al. used an NFAT-controlled green fluorescent protein (GFP) reporter to monitor NFAT-induced gene expression in single cells. Store depletion with the pharmacological agent thapsigargin or the proinflammatory molecule leukotriene C4 (LTC4), both of which trigger CRAC channel activity, caused an all-or-none response of individual cells in terms of GFP induction, but the number of cells that responded depended on the strength of the stimulating signal. Thus, the individual cellular response was all or none, whereas the population response was graded. Furthermore, the cells responded to two pulses of LTC4 with nuclear translocation of NFAT and induction of GFP, but only if those two pulses were sufficiently close together, suggesting that NFAT serves as a coincidence detector. Thus, the authors propose that sequential stimuli allow sufficient dephosphorylation of NFAT to enable its nuclear translocation. Rapid CRAC-induced calcium oscillations contribute to a cellular memory response manifested hours later as a change in gene expression, which only occurs if the stimuli producing the signals are received sufficiently close together.

P. Kar, C. Nelson, A. B. Parekh, CRAC channels drive digital activation and provide analog control and synergy to Ca2+-dependent gene regulation. Curr. Biol. 22, 242–247 (2012). [PubMed]

J. W. Putney, Calcium signaling: Deciphering the calcium–NFAT pathway. Curr. Biol. 22, R87–R89 (2012). [PubMed]

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