Modeling domain formation of MARCKS and protein kinase C at cellular membranes

Background: Phosphorylation and dephosphorylation of proteins are mechanisms of activation and deactivation which regulate many cellular processes. Both mechanisms have been usually described in well mixed environments. MARCKS is a protein which binds to the membrane by electrostatic interaction. It is translocated from the membrane and phosphorylated by Protein Kinase C. Back in the cytoplasm the translocated MARCKS proteins are dephosphorylated by the enzyme phosphatase and can reattach to the membrane. These three processes (membrane binding, translocation, dephosphorylation) give rise to a cyclic dynamics known as the myristoyl-electrostatic switch. Methods: We employ a reaction-diffusion model for the concentrations of MARCKS and PKC in the cell in a circular domain. Results: Herein, we start from a reaction-diffusion model taking into account mass conservation of the MARCKS proteins. Then, we extend the model by including the dynamics of binding and unbinding of PKC enzymes, which are in turn activated by spikes of calcium. Furthermore, we show that the model fits previous experimental results well and predicts, in addition, the formation of domains with high concentration of MARCKS proteins at the membrane. Conclusions: We have developed a simple model of binding, phosphorylation and desphosphorylation for MARCKS protein. The main prediction emerging from numerical simulations of the model is the spontaneous appearance of domains of high concentration of membrane proteins.