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BIOMD0000000354 - Abell2011_CalciumSignaling_WithoutAdaptation

 

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Reference Publication
Publication ID: 21844332
Abell E, Ahrends R, Bandara S, Park BO, Teruel MN.
Parallel adaptive feedback enhances reliability of the Ca2+ signaling system.
Proc. Natl. Acad. Sci. U.S.A. 2011 Aug; 108(35): 14485-14490
Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.  [more]
Model
Original Model: Meyer1991_CalciumSpike_ICC
Submitter: Samuel Bandara
Submission ID: MODEL1108050000
Submission Date: 05 Aug 2011 01:15:12 UTC
Last Modification Date: 08 Sep 2011 12:16:51 UTC
Creation Date: 17 Aug 2011 15:56:29 UTC
Encoders:  Vijayalakshmi Chelliah
   Mary N Teruel
set #1
bqbiol:occursIn Taxonomy Drosophila
set #2
bqbiol:isVersionOf Gene Ontology calcium-mediated signaling
Notes

This model is from the article:
Parallel adaptive feedback enhances reliability of the Ca2+ signaling system.
Abell E, Ahrends R, Bandara S, Park BO, Teruel MN. Proc Natl Acad Sci U S A. 2011 Aug 15. 21844332 ,
Abstract:
Despite large cell-to-cell variations in the concentrations of individual signaling proteins, cells transmit signals correctly. This phenomenon raises the question of what signaling systems do to prevent a predicted high failure rate. Here we combine quantitative modeling, RNA interference, and targeted selective reaction monitoring (SRM) mass spectrometry, and we show for the ubiquitous and fundamental calcium signaling system that cells monitor cytosolic and endoplasmic reticulum (ER) Ca(2+) levels and adjust in parallel the concentrations of the store-operated Ca(2+) influx mediator stromal interaction molecule (STIM), the plasma membrane Ca(2+) pump plasma membrane Ca-ATPase (PMCA), and the ER Ca(2+) pump sarco/ER Ca(2+)-ATPase (SERCA). Model calculations show that this combined parallel regulation in protein expression levels effectively stabilizes basal cytosolic and ER Ca(2+) levels and preserves receptor signaling. Our results demonstrate that, rather than directly controlling the relative level of signaling proteins in a forward regulation strategy, cells prevent transmission failure by sensing the state of the signaling pathway and using multiple parallel adaptive feedbacks.

Note:

There are two models described in the paper to simulate basal and receptor stimulated Ca 2+ signaling. 1) No adaptive feedback (this model: MODEL1108050000) and 2) with three slow adaptive feedback loops (MODEL1108050001).

Model
Publication ID: 21844332 Submission Date: 05 Aug 2011 01:15:12 UTC Last Modification Date: 08 Sep 2011 12:16:51 UTC Creation Date: 17 Aug 2011 15:56:29 UTC
Mathematical expressions
Reactions
PLC: Receptor and Ca2+ regulated IP3 production SERCA: Pumps Ca2+ into ER Ca2+ stores IP3R: IP3 and Ca2+ regulated Ca2+ channel, plus leak IP3 phosphatase: Degradation of IP3
Inhibition of IP3R (mechanism not well understood) Recovery of IP3R from Ca2+ iinhibition when Ca2+ drops Regulation of Orai by STIM, plus leak PMCA: Pumps Ca2+ across PM out of cell
UniporterFromCytosol MitoToCytosol ERtoMito  
Physical entities
Compartments Species
cytosol CaI IP3 g
     
Outside CaO    
ER_store CaS    
mito CaM    
Global parameters
IP3R SERCA IP3degradation IP3Rinhibition
IP3Rrecovery kSERCA ERleak R
kIP3R PMleak kSTIM STIM
kIP3Rca kPMCA PMCA kG
DirTransf MitNaCaEx UniPort kUniP
Reactions (11)
 
 PLC: Receptor and Ca2+ regulated IP3 production  → [IP3];   {CaI}
 
 SERCA: Pumps Ca2+ into ER Ca2+ stores [CaI] → [CaS];  
 
 IP3R: IP3 and Ca2+ regulated Ca2+ channel, plus leak [CaS] → [CaI];   {g} , {IP3}
 
 IP3 phosphatase: Degradation of IP3 [IP3] → ;  
 
 Inhibition of IP3R (mechanism not well understood)  → [g];   {CaI}
 
 Recovery of IP3R from Ca2+ iinhibition when Ca2+ drops [g] → ;  
 
 Regulation of Orai by STIM, plus leak  → [CaI];   {CaS}
 
 PMCA: Pumps Ca2+ across PM out of cell [CaI] → ;  
 
 UniporterFromCytosol [CaI] → [CaM];  
 
 MitoToCytosol [CaM] → [CaI];  
 
 ERtoMito [CaS] → [CaM];   {CaI} , {g} , {IP3}
 
 cytosol Spatial dimensions: 3.0  Compartment size: 1.0
 
 CaI
Compartment: cytosol
Initial amount: 0.05
 
 IP3
Compartment: cytosol
Initial amount: 0.0
 
 g
Compartment: cytosol
Initial amount: 0.0020
 
 Outside Spatial dimensions: 3.0  Compartment size: 1.0
 
 CaO
Compartment: Outside
Initial amount: 1000.0
 
 ER_store Spatial dimensions: 3.0  Compartment size: 1.0
 
 CaS
Compartment: ER_store
Initial amount: 2.0
 
 mito Spatial dimensions: 3.0  Compartment size: 1.0
 
 CaM
Compartment: mito
Initial amount: 0.0
 
Global Parameters (20)
 
   IP3R
Value: 3.0
Constant
 
   SERCA
Value: 0.266
Constant
 
   IP3degradation
Value: 2.0
Constant
 
   IP3Rinhibition
Value: 5.0
Constant
 
   IP3Rrecovery
Value: 0.018
Constant
 
   kSERCA
Value: 0.175
Constant
 
   ERleak
Value: 0.01
Constant
 
   R
Value: 1.0
Constant
 
   kIP3R
Value: 0.175
Constant
 
   PMleak
Value: 0.0346
Constant
 
   kSTIM
Value: 1.0
Constant
 
   STIM
Value: 0.02
Constant
 
   kIP3Rca
Value: 0.13
Constant
 
   kPMCA
Value: 0.2
Constant
 
   PMCA
Value: 0.013
Constant
 
   kG
Value: 1.0
Constant
 
   DirTransf
Value: 0.03
Constant
 
   MitNaCaEx
Value: 0.0050
Constant
 
   UniPort
Value: 0.03
Constant
 
   kUniP
Value: 0.6
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000354

Curator's comment: (updated: 17 Aug 2011 16:54:43 BST)

There are two models described in the paper to simulate basal and receptor stimulated Ca2+ signaling. 1) No adaptive feedback (this model: MODEL1108050000) and 2) with three slow adaptive feedback loops (MODEL1108050001).
Figure 1B (which shows the simulation of cytosolic Calcium (CaI) at different levels of receptor activation) of the reference article has been reproduced here. The corresponding R value for 15%, 27%, 42% and 75% are 0.39286, 0.70714, 1.1 and 1.96428 respectively, the maximum R value being 2.61905.
The model has also been tested for a range of R values 0-100%, and the results were consistent with that of figure 1C (Control). For the R range 1) between 0% and 22.5% there was no signal, 2) between 22.5% and 49% triggered Calicum oscillations and 3) between 49% and 100% induced the plateau phase.
The model was integrated and simulated using Copasi v4.7 (Build 34). Data were obtained from Copasi and plotted using Gnuplot.

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