Selective Regulation of Cellular Processes by Complex Ca²⁺ Signals

Marko Marhl, Beate Knoke, Stefan Schuster

Dept. of Phyiscs, Faculty of Education, University of Maribor; Dept. of Bioinformatics, Faculty of Biology and Pharmaceutics, Friedrich-Schiller University of Jena

Calcium plays important role in intracellular signal transduction. As a second messenger, it represents a link between several input signals and several target processes in the cell. After stimulating a cell by an agonist, like a hormone or neurotransmitter, the concentration of Ca²⁺ in the cytosol is elevated. The cytosolic Ca²⁺ concentration can change periodically in time, and the pattern of the Ca²⁺ oscillations depends strongly on the agonist concentration. Recently it has been shown experimentally that the carrying information can be encoded by the frequency of Ca²⁺ oscillations (De Koninck and Schulman, Science 279 (1998), 227-230). Whereas the frequency of simple spiking Ca²⁺ oscillations enables a selective activation of a specific protein and herewith a specific cellular process, the question arises how at the same time two or more classes of proteins can be selectively activated. The question is general and concerns the problem of how one second messenger can transmit more than one signal simultaneously (bow-tie structure of signalling). The results of our theoretical study indicate that complex bursting Ca²⁺ oscillations can perform the function of simultaneous transmission of two signals by selective activation of two calcium-binding proteins. We show that in dependence on the bursting pattern, a succession of low-peak and high-peak oscillatory phases, one protein can be gradually activated at a constant level of the other protein’s activity, or the two proteins can be activated simultaneously, or one protein can be activated while the other one is deactivated simultaneously. Thus, the two proteins linked to two different cellular processes can be regulated independently.

Email: marko.marhl@uni-mb.si

Address: Department of Physics, Faculty of Education, University of Maribor,, Koroška cesta 160, SI-2000 Maribor, Slovenia