public model
Short description
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.

This model has been generated by VCell

This model is described in the article:

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.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V1)
Related Publication
  • Kinetic analysis of receptor-activated phosphoinositide turnover.
  • Xu C, Watras J, Loew LM
  • The Journal of cell biology , 5/ 2003 , Volume 161 , pages: 779-791
  • Department of Physiology, University of Connecticut Health Center, Farmington, CT 06030, USA.
  • 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.
Contributors
Harish Dharuri

Metadata information

is
BioModels Database MODEL3095606944
BioModels Database BIOMD0000000075
isDescribedBy
PubMed 12771127
isDerivedFrom
PubMed 10579714
PubMed 10866945
hasTaxon
Taxonomy Mus musculus
isVersionOf
occursIn
Brenda Tissue Ontology neuroblastoma cell
Curation status
Curated
Original model(s)
http://www.nrcam.uchc.edu/applications/access_models/xu.html
  • Model originally submitted by : Harish Dharuri
  • Submitted: 09-Nov-2006 21:33:05
  • Last Modified: 08-Apr-2016 16:33:07
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 08-Apr-2016 16:33:07
    • Submitted by: Harish Dharuri
    • With comment: Current version of Xu2003 - Phosphoinositide turnover
  • Version: 1 public model Download this version
    • Submitted on: 09-Nov-2006 21:33:05
    • Submitted by: Harish Dharuri
    • With comment: Original import of Xu2003_Phosphoinositide_turnover
Curator's comment:
(added: 19 Dec 2006, 00:27:27, updated: 19 Dec 2006, 00:27:27)
The plots above correspond to Fig1 of the paper. Results obtained with MathSBML.