Editors' ChoiceCalcium signaling

New connections: Interpreting calcium signals

Sci. Signal.  23 Feb 2016:
Vol. 9, Issue 416, pp. ec42
DOI: 10.1126/scisignal.aaf5093

This week’s issue of Science Signaling includes a paper by Noren et al. that describes how endothelial cells use different patterns of Ca2+ signals to produce different cellular responses to the same stimulus. The authors rely on single-cell analysis and computational approaches to dissect Ca2+ signal patterns triggered by vascular endothelial growth factor (VEGF), which caused either migration or proliferation of the endothelial cells. They then relate their findings to sprouting angiogenesis in zebrafish. In an earlier paper, Pászty et al. also studied endothelial cells to determine the importance of the plasma membrane Ca2+ ATPases in shaping Ca2+ signals triggered by depletion of Ca2+ from the endoplasmic reticulum [store-operated calcium entry (SOCE)]. A similar type of single-cell analysis was previously used by Thurley et al. to explore randomness and variability in Ca2+ signals in individual hepatocytes within a population of cells responding to activation of α-adrenergic receptors. Mathematical analysis revealed a mechanism by which the cells interpret a common change in a random component of the Ca2+ pattern so that the population correctly interprets changes in the frequency of the Ca2+ spikes as an indication of the strength of the stimulus. These papers are excellent examples of how the application of single-cell analysis and computational approaches can be used to investigate how cells interpret a dynamic signal.

D. P. Noren, W. H. Chou, S. H. Lee, A. A. Qutub, A. Warmflash, D. S. Wagner, A. S. Popel, A. Levchenko, Endothelial cells decode VEGF-mediated Ca2+ signaling patterns to produce distinct functional responses. Sci. Signal. 9, ra20 (2016). [Abstract]

K. Pászty, A. J. Caride, Ž. Bajzer, C. P. Offord, R. Padányi, L. Hegedűs, K. Varga, E. E. Strehler, A. Enyedi, Plasma membrane Ca2+-ATPases can shape the pattern of Ca2+ transients induced by store-operated Ca2+ entry. Sci. Signal. 8, ra19 (2015). [Abstract]

K. Thurley, S. C. Tovey, G. Moenke, V. L. Prince, A. Meena, A. P. Thomas, A. Skupin, C. W. Taylor, M. Falcke, Reliable encoding of stimulus intensities within random sequences of intracellular Ca2+ spikes. Sci. Signal. 7, ra59 (2014). [Abstract]