Localized activation of proteins in a free intracellular space: Dependence of cellular morphologies and reaction schemes

Abstract

Localized activation of proteins in a cell is crucial for the segregation of cellular functions leading, for example, to the development of polarized cells and chemotaxis. If there is a physical diffusion barrier, localized activation of proteins will emerge. In case of no physical barrier, however, it is not clear to what extent the protein activation is localized within a three dimensional intracellular space. In the previous report we showed a simulation result of localized activation of Ca 2+/calmodulin-dependent kinase II (CaMKII) within a dendritic spine of a neuron, and this localization was enhanced by the diffusion of calmodulin. However, a dendritic spine will act as a physical diffusion barrier. Here, we report that the localization of activated proteins is seen in more simplified morphology with no diffusion barrier. Furthermore, this localization was seen with a simple reaction scheme. In case that a Ca 2+ source was located at the center of the spherical cell with diameter of 20 μm, which is the extreme case without any physical diffusion barrier, the simulation results showed localized activation of a protein around the Ca 2+ source. This localized activation was also enhanced by the diffusion of calmodulin. These localizations were not blurred with time within the tested time range. The reason for the increase in the localization by the diffusion of calmodulin was the replenishment of free calmodulin from surrounding regions. These simulation results indicate that the localized activation of proteins emerges in biological cells without any physical diffusion barrier, and the replenishment of proteins by diffusion can act as an enhancer of localized activation of downstream proteins.