Abstract

BackgroundCalcium signalling relies on the flux of calcium ions across membranes yet how signals in different compartments are related remains unclear. In particular, similar calcium signals on both sides of the nuclear envelope have been reported and attributed to passive diffusion through nuclear pores. However, observed differing cytosolic and nucleosolic calcium signatures suggest that the signalling machinery in these compartments can act independently.ResultsWe adapt the fire-diffuse-fire model to investigate the generation of perinuclear calcium oscillations. We demonstrate that autonomous spatio-temporal calcium patterns are still possible in the presence of nuclear and cytosolic coupling via nuclear pores. The presence or absence of this autonomy is dependent upon the strength of the coupling and the maximum firing rate of an individual calcium channel. In all cases, coupling through the nuclear pores enables robust signalling with respect to changes in the diffusion constant.ConclusionsWe show that contradictory interpretations of experimental data with respect to the autonomy of nuclear calcium oscillations can be reconciled within one model, with different observations being a consequence of varying nuclear pore permeabilities for calcium and refractory conditions of channels. Furthermore, our results provide an explanation for why calcium oscillations on both sides of the nuclear envelope may be beneficial for sustained perinuclear signaling.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-016-0289-9) contains supplementary material, which is available to authorized users.

Highlights

  • Calcium signalling relies on the flux of calcium ions across membranes yet how signals in different compartments are related remains unclear

  • We show that the coupling between the nucleus and cytosol is a key ingredient for the robustness of perinuclear Ca2+ oscillations with respect to changes in the diffusion constant of Ca2+, but that this coupling may allow for autonomous Ca2+ signatures on either side of the nuclear envelope (NE)

  • If there were no pores present as illustrated in the grey region of Fig. 2, the maximum concentration of Ca2+ measured at PN would be twice the value measured before. This happens if channel C had released the same amount of Ca2+

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Summary

Introduction

Calcium signalling relies on the flux of calcium ions across membranes yet how signals in different compartments are related remains unclear. Observed differing cytosolic and nucleosolic calcium signatures suggest that the signalling machinery in these compartments can act independently. Changes in the concentration of free calcium ions (Ca2+) within cellular compartments [1,2,3] can act as a key information carrier in plants and animals [4,5,6]. The existence of calcium transients in isolated nuclei [30,31,32], significant delays and persistent gradients between cytosolic and nuclear transients [33], and the observation that different stimuli can selectively activate. Martins et al BMC Systems Biology (2016) 10:55 only one of the compartments [33] suggests that cytosolic and nucleosolic calcium levels are independently regulated. Free Ca2+ passage through permeable pores provides an additional source of calcium, and questions the independence of nuclear Ca2+ signalling

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