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BIOMD0000000075 - Xu2003 - Phosphoinositide turnover

 

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Reference Publication
Publication ID: 12771127
Xu C, Watras J, Loew LM.
Kinetic analysis of receptor-activated phosphoinositide turnover.
J. Cell Biol. 2003 May; 161(4): 779-791
Department of Physiology, University of Connecticut Health Center, Farmington, CT 06030, USA.  [more]
Model
Original Model: VCell logo
Submitter: Harish Dharuri
Submission ID: MODEL3095606944
Submission Date: 09 Nov 2006 21:33:05 UTC
Last Modification Date: 24 May 2014 17:11:16 UTC
Creation Date: 23 Oct 2008 00:38:38 UTC
Encoders:  Harish Dharuri
   Nick Juty
set #1
bqmodel:isDerivedFrom PubMed 10866945
PubMed 10579714
set #2
bqbiol:hasTaxon Taxonomy Mus musculus
set #3
bqbiol:isPartOf KEGG Pathway Phosphatidylinositol signaling system
bqbiol:isVersionOf Gene Ontology phosphatidylinositol metabolic process
bqbiol:occursIn Brenda Tissue Ontology neuroblastoma cell
Notes
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.

Model
Publication ID: 12771127 Submission Date: 09 Nov 2006 21:33:05 UTC Last Modification Date: 24 May 2014 17:11:16 UTC Creation Date: 23 Oct 2008 00:38:38 UTC
Mathematical expressions
Reactions
PIPSyn PIP2_hyd PLCact PIP2_PH_hyd
PIP2_PH IP3deg PIP2Syn IP3-PHGFP
Rules
Assignment Rule (variable: Ratebasal_PIPsyn_PIPSyn) Assignment Rule (variable: Ratestim_PIPsyn_PIPSyn) Assignment Rule (variable: signal_PLCact) Assignment Rule (variable: kr_PIP2PH_PIP2_PH)
Assignment Rule (variable: Rate_PIP2Synbasal_PIP2Syn) Assignment Rule (variable: Rate_PIP2SynStim_PIP2Syn) Assignment Rule (variable: kr_IP3PH_IP3_PHGFP)  
Physical entities
Compartments Species
Extracellular      
PM PIP2_PHGFP_PM PI_PM stim_PM
PIP2_PM PIP_PM DAG_PM
PLC_PM PLC_act_PM  
Cytosol PH_GFP_Cyt IP3_PHGFP_Cyt hv_Cytosol
IP3X_Cytosol IP3_Cyt  
NM      
Nucleus      
Global parameters
KMOLE PIP_basal_PIPSyn kBasalSynPIP_PIPSyn kStimSynPIP_PIPSyn
tauPIPsyn_PIPSyn PIPsyndecay_PIPSyn Ratebasal_PIPsyn_PIPSyn Ratestim_PIPsyn_PIPSyn
tau0_PLCact stimdecay_PLCact signal_PLCact kf_PIP2PH_PIP2_PH
KdPIP2PH_PIP2_PH kr_PIP2PH_PIP2_PH kStimSynPIP2_PIP2Syn tauPIP2syn_PIP2Syn
PIP2syndecay_PIP2Syn PIP2_basal_PIP2Syn kBasalSynPIP2_PIP2Syn Rate_PIP2Synbasal_PIP2Syn
Rate_PIP2SynStim_PIP2Syn kf_IP3PH_IP3_PHGFP KdIP3PH_IP3_PHGFP kr_IP3PH_IP3_PHGFP
Reactions (8)
 
 PIPSyn [PI_PM] ↔ [PIP_PM];  
 
 PIP2_hyd [PIP2_PM] ↔ [DAG_PM] + [IP3_Cyt];   {PLC_act_PM}
 
 PLCact [PLC_PM] ↔ [PLC_act_PM];   {stim_PM}
 
 PIP2_PH_hyd [PIP2_PHGFP_PM] ↔ [PH_GFP_Cyt] + [IP3_Cyt] + [DAG_PM];   {PLC_act_PM}
 
 PIP2_PH [PH_GFP_Cyt] + [PIP2_PM] ↔ [PIP2_PHGFP_PM];  
 
 IP3deg [IP3_Cyt] ↔ ;  
 
 PIP2Syn [PIP_PM] ↔ [PIP2_PM];  
 
 IP3-PHGFP [IP3_Cyt] + [PH_GFP_Cyt] ↔ [IP3_PHGFP_Cyt];  
 
Rules (7)
 
 Assignment Rule (name: Ratebasal_PIPsyn_PIPSyn) Ratebasal_PIPsyn_PIPSyn = piecewise(0.581*kBasalSynPIP_PIPSyn*(-1+exp((PIP_basal_PIPSyn+(-PIP_PM))*1/PIP_basal_PIPSyn)), PIP_PM < PIP_basal_PIPSyn, 0)
 
 Assignment Rule (name: Ratestim_PIPsyn_PIPSyn) Ratestim_PIPsyn_PIPSyn = piecewise(kStimSynPIP_PIPSyn*exp(-(t+(-tauPIPsyn_PIPSyn))*1/PIPsyndecay_PIPSyn), t > tauPIPsyn_PIPSyn, 0)
 
 Assignment Rule (name: signal_PLCact) signal_PLCact = piecewise(exp(-(t+(-tau0_PLCact))*1/stimdecay_PLCact), t > tau0_PLCact, 0)
 
 Assignment Rule (name: kr_PIP2PH_PIP2_PH) kr_PIP2PH_PIP2_PH = kf_PIP2PH_PIP2_PH*KdPIP2PH_PIP2_PH
 
 Assignment Rule (name: Rate_PIP2Synbasal_PIP2Syn) Rate_PIP2Synbasal_PIP2Syn = piecewise(0.581*kBasalSynPIP2_PIP2Syn*(-1+exp((PIP2_basal_PIP2Syn+(-PIP2_PM))*1/PIP2_basal_PIP2Syn)), PIP2_PM < PIP2_basal_PIP2Syn, 0)
 
 Assignment Rule (name: Rate_PIP2SynStim_PIP2Syn) Rate_PIP2SynStim_PIP2Syn = piecewise(kStimSynPIP2_PIP2Syn*exp(-(t+(-tauPIP2syn_PIP2Syn))*1/PIP2syndecay_PIP2Syn), t > tauPIP2syn_PIP2Syn, 0)
 
 Assignment Rule (name: kr_IP3PH_IP3_PHGFP) kr_IP3PH_IP3_PHGFP = kf_IP3PH_IP3_PHGFP*KdIP3PH_IP3_PHGFP
 
 Extracellular Spatial dimensions: 3.0  Compartment size: 0.277777777777778
 PM Spatial dimensions: 2.0  Compartment size: 0.5555555555556  (Units: um2)
 
 PIP2_PHGFP_PM
Compartment: PM
Initial concentration: 0.0  (Units: molecules)
 
 PI_PM
Compartment: PM
Initial concentration: 142857.0  (Units: molecules)
 
 stim_PM
Compartment: PM
Initial concentration: 1.0  (Units: molecules)
 
 PIP2_PM
Compartment: PM
Initial concentration: 4000.0  (Units: molecules)
 
 PIP_PM
Compartment: PM
Initial concentration: 2857.0  (Units: molecules)
 
 DAG_PM
Compartment: PM
Initial concentration: 2000.0  (Units: molecules)
 
 PLC_PM
Compartment: PM
Initial concentration: 100.0  (Units: molecules)
 
 PLC_act_PM
Compartment: PM
Initial concentration: 0.0  (Units: molecules)
 
 Cytosol Spatial dimensions: 3.0  Compartment size: 1.0
 
 PH_GFP_Cyt
Compartment: Cytosol
Initial concentration: 0.0  (Units: molecules)
 
 IP3_PHGFP_Cyt
Compartment: Cytosol
Initial concentration: 0.0  (Units: molecules)
 
 hv_Cytosol
Compartment: Cytosol
Initial concentration: 0.0  (Units: molecules)
 
 IP3X_Cytosol
Compartment: Cytosol
Initial concentration: 0.0  (Units: molecules)
 
 IP3_Cyt
Compartment: Cytosol
Initial concentration: 96.32  (Units: molecules)
 
 NM Spatial dimensions: 2.0  Compartment size: 0.111111111111111  (Units: um2)
 Nucleus Spatial dimensions: 3.0  Compartment size: 0.111111111111111
Global Parameters (24)
 
   KMOLE
Value: 0.00166112956810631   (Units: uM_um3_molecules_1)
Constant
 
   PIP_basal_PIPSyn
Value: 2857.0   (Units: molecules_um_2)
Constant
 
   kBasalSynPIP_PIPSyn
Value: 0.0055   (Units: s_1)
Constant
 
   kStimSynPIP_PIPSyn
Value: 0.019   (Units: s_1)
Constant
 
   tauPIPsyn_PIPSyn
Value: 0.05   (Units: s)
Constant
 
   PIPsyndecay_PIPSyn
Value: 1.0   (Units: s)
Constant
 
   Ratebasal_PIPsyn_PIPSyn
Value: NaN   (Units: s_1)
 
   Ratestim_PIPsyn_PIPSyn
Value: NaN   (Units: s_1)
 
   tau0_PLCact
Value: 0.05   (Units: second)
Constant
 
   stimdecay_PLCact
Value: 1.0   (Units: second)
Constant
 
   signal_PLCact
Value: NaN   (Units: dimensionless)
 
   kf_PIP2PH_PIP2_PH
Value: 0.12   (Units: uM_1_s_1)
Constant
 
   KdPIP2PH_PIP2_PH
Value: 2.0   (Units: uM)
Constant
 
   kr_PIP2PH_PIP2_PH
Value: NaN   (Units: s_1)
 
   kStimSynPIP2_PIP2Syn
Value: 0.92   (Units: s_1)
Constant
 
   tauPIP2syn_PIP2Syn
Value: 0.05   (Units: s)
Constant
 
   PIP2syndecay_PIP2Syn
Value: 1.0   (Units: s)
Constant
 
   PIP2_basal_PIP2Syn
Value: 4000.0   (Units: molecules_um_2)
Constant
 
   kBasalSynPIP2_PIP2Syn
Value: 0.048   (Units: s_1)
Constant
 
   Rate_PIP2Synbasal_PIP2Syn
Value: NaN   (Units: s_1)
 
   Rate_PIP2SynStim_PIP2Syn
Value: NaN   (Units: s_1)
 
   kf_IP3PH_IP3_PHGFP
Value: 10.0   (Units: uM_1_s_1)
Constant
 
   KdIP3PH_IP3_PHGFP
Value: 2.0   (Units: uM)
Constant
 
   kr_IP3PH_IP3_PHGFP
Value: NaN   (Units: s_1)
 
PIPSyn (1)
 
   I
Constant
 
PIP2_hyd (2)
 
   I
Constant
 
   k_PIP2hyd
Value: 2.4   (Units: um2_molecules_1_s_1)
Constant
 
PLCact (3)
 
   I
Constant
 
   KfPLCact
Value: 5.0E-4   (Units: um2_molecules_1_s_1)
Constant
 
   krPLCact
Value: 0.1   (Units: s_1)
Constant
 
PIP2_PH_hyd (2)
 
   I
Constant
 
   k_PIP2PHhyd
Constant
 
PIP2_PH (1)
 
   I
Constant
 
IP3deg (2)
 
   kIP3deg
Value: 0.08   (Units: s_1)
Constant
 
   IP3_basal
Value: 0.16   (Units: uM)
Constant
 
PIP2Syn (1)
 
   I
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000075

Curator's comment: (updated: 19 Dec 2006 00:27:27 GMT)

The plots above correspond to Fig1 of the paper. Results obtained with MathSBML.

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