Four universal modules and their combinations for decoding amplitude and frequency of Ca²⁺ signals in plants

Calcium signals are fundamental for plants and play crucial roles in developmental processes and in rapid responses to environmental stimuli and stress factors. Nevertheless, the mechanisms underlying the decoding of calcium signals in plants are still largely unclear. We have addressed the question of Ca²⁺ signal decoding in a bottom-up modelling approach starting with the thermodynamics of Ca²⁺ binding to EF hands (EF: Glutamic acid-Phenylalanine) in Ca²⁺-binding proteins (CBPs). On this basis, we identified four universal, fundamental Ca²⁺ decoding modules, in which a CBP modulates the activity of a target protein (TP). Representatives of these basic modules are omnipresent in plant cells. Their Ca²⁺ dependent properties are mainly determined by the interaction of the CBP with the TP rather than the Ca²⁺-binding properties of the EF hands. Combinations of the modules generated complexes that are also observed in plants, which decode not only the amplitude but also the frequency of Ca²⁺ signals by setting specific 'frequency islands' in which a TP is active. The modelling approach presented here addresses the decoding of Ca²⁺ signals from the microscopic to the systemic level and could help to find the 'Rosetta Stone' for Ca²⁺ signalling in plants.