Xu2003 - Phosphoinositide turnover

Xu2003 - Phosphoinositide turnover

The model reproduces the percentage change of PIP_PM, PIP2_PM and IP3_Cyt as depicted in Figure 1 of the paper. The model also contains the equations for the analysis of PH-GFP experiments, however the initial value of PH_GFP has been set to zero to more accurately reproduce Figure 1. The units of cytosolic species are given in molecules/um^3. In order to convert them to uM, divide the concentration by 602. For the analysis of PH_GFP experiments, one should plug in the values of PH_GFP, IP3_PHGFP and PIP2_PHGFP from Table AI in the appendix. The model was successfully tested on MathSBML.

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This model is described in the article:

Kinetic analysis of receptor-activated phosphoinositide turnover.

Xu C, Watras J, Loew LM.
J. Cell Biol. 2003 May; 161(4): 779-791
Abstract:

We studied the bradykinin-induced changes in phosphoinositide composition of N1E-115 neuroblastoma cells using a combination of biochemistry, microscope imaging, and mathematical modeling. Phosphatidylinositol-4,5-bisphosphate (PIP2) decreased over the first 30 s, and then recovered over the following 2-3 min. However, the rate and amount of inositol-1,4,5-trisphosphate (InsP3) production were much greater than the rate or amount of PIP2 decline. A mathematical model of phosphoinositide turnover based on this data predicted that PIP2 synthesis is also stimulated by bradykinin, causing an early transient increase in its concentration. This was subsequently confirmed experimentally. Then, we used single-cell microscopy to further examine phosphoinositide turnover by following the translocation of the pleckstrin homology domain of PLCdelta1 fused to green fluorescent protein (PH-GFP). The observed time course could be simulated by incorporating binding of PIP2 and InsP3 to PH-GFP into the model that had been used to analyze the biochemistry. Furthermore, this analysis could help to resolve a controversy over whether the translocation of PH-GFP from membrane to cytosol is due to a decrease in PIP2 on the membrane or an increase in InsP3 in cytosol; by computationally clamping the concentrations of each of these compounds, the model shows how both contribute to the dynamics of probe translocation.

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