BIOMD0000000355
type: SBMLModel
parameter: 032055
reaction: 032024
species: 031976
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 (MODEL1108050000) and 2) with three slow adaptive feedback loops (this model: MODEL1108050001).
parameter: 032035
parameter: 032063
parameter: 032073
created:
  W3 CDTF: Wed Aug 17 16:57:15 BST 2011
reaction: 031996
is version of: GO:0019722
species: 031986
compartment: 031966
reaction: 032014
reaction: 031992
compartment: 031970
parameter: 032045
compartment: 031969
reaction: 032022
parameter: 032071
parameter: 032069
reaction: 031998
species: 031984
reaction: 032016
is: MODEL1108050001
is described by: http://identifiers.org/pubmed/21844332
parameter: 032043
parameter: 032053
parameter: 032059
species: 031974
substance units: metaid_0000076
parameter: 032033
species: 031982
parameter: 032061
name: Abell2011_CalciumSignaling_WithAdaptation
reaction: 032018
parameter: 032067
area units: 498119
length unit: length
time units: metaid_0000075
reaction: 032002
reaction: 032012
parameter: 032051
parameter: 032049
reaction: 032020
species: 031990
species: 031978
parameter: 032031
occurs in: http://identifiers.org/taxonomy/7215
reaction: 032008
curated: true
reaction: 032004
species: 031988
volume units: 498095
reaction: 032010
modified:
  W3 CDTF: Thu Sep 08 13:03:57 BST 2011
parameter: 032041
parameter: 032047
parameter: 032057
species: 031980
parameter: 032037
reaction: 032006
creator:
  ORG:
    orgname: Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305
  n:
    given: Mary N
    family: Teruel
parameter: 032065
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Vijayalakshmi
    family: Chelliah
compartment: 031972
reaction: 032000
reaction: 031994
parameter: 032039

032055
type: Parameter
constant: true
value: 0.13
name: kIP3Rca

032024
type: Reaction
kinetic law: 524780
product: 524768
reactant: 524756
is version of: GO:0006851
fast: false
reversible: false
name: MitoToCytosol

524768
type: SpeciesReference
stoichiometry: 1.0
species: 031974

031974
type: Species
is: SBO:0000247
initial concentration: NaN
has only substance units: false
name: CaI
constant: false
is version of: CHEBI:29108
boundary condition: false
in compartment: 031966
is version of: C00076
initial amount: 0.05

031966
type: Compartment
is version of: GO:0005829
is: SBO:0000290
constant: false
size: 1.0
spatial dimensions: 3.0
name: cytosol

524756
type: SpeciesReference
stoichiometry: 1.0
species: 031988

031988
type: Species
initial concentration: NaN
name: CaM
is version of: CHEBI:29108
is: SBO:0000247
constant: false
is version of: C00076
initial amount: 0.0
boundary condition: false
in compartment: 031970
has only substance units: false

031970
type: Compartment
is version of: GO:0005739
is: SBO:0000290
constant: true
size: 1.0
spatial dimensions: 3.0
name: mito

031976
type: Species
initial amount: 0.0
is version of: CHEBI:16595
initial concentration: NaN
constant: false
has only substance units: false
is version of: C01255
name: IP3
boundary condition: false
is: SBO:0000247
in compartment: 031966

032035
type: Parameter
constant: true
value: 2.0
name: IP3degradation

032063
type: Parameter
constant: true
value: 1.0E-6
name: ProtDeg

032073
type: Parameter
constant: true
value: 8.0
name: cr

031996
type: Reaction
product: 524237
modifier: 524249
is version of: GO:0051209
name: IP3R: IP3 and Ca2+ regulated Ca2+ channel, plus leak
fast: false
reactant: 524225
modifier: 524261
reversible: false
kinetic law: 524273

524237
type: SpeciesReference
stoichiometry: 1.0
species: 031974

031978
type: Species
is version of: GO:0019855
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.002
in compartment: 031966
name: g

524225
type: SpeciesReference
stoichiometry: 1.0
species: 031990

031990
type: Species
initial concentration: NaN
in compartment: 031972
boundary condition: false
is version of: CHEBI:29108
has only substance units: false
name: CaS
is version of: C00076
constant: false
initial amount: 2.0
is: SBO:0000247

031972
type: Compartment
is version of: GO:0005783
is: SBO:0000290
constant: false
size: 1.0
spatial dimensions: 3.0
name: ER_store

031986
type: Species
is version of: CHEBI:29108
is: SBO:0000247
initial concentration: NaN
boundary condition: false
has only substance units: false
name: CaO
constant: false
initial amount: 1000.0
is version of: C00076
in compartment: 031969

031969
type: Compartment
is version of: GO:0005576
is: SBO:0000290
constant: true
size: 1.0
spatial dimensions: 3.0
name: Outside

032014
type: Reaction
kinetic law: 524587
modifier: 524575
modifier: 524563
product: 524551
is version of: GO:0009058
fast: false
reversible: false
name: STIM/Orai synthesis

524551
type: SpeciesReference
stoichiometry: 1.0
species: 031984

031984
type: Species
is version of: P83094
is: SBO:0000252
initial amount: 0.02
initial concentration: NaN
name: STIM
in compartment: 031966
constant: false
boundary condition: false
has only substance units: false

031992
type: Reaction
kinetic law: 524164
modifier: 524152
product: 524139
is version of: GO:0032959
fast: false
reversible: false
name: PLC: Receptor and Ca2+ regulated IP3 production

524139
type: SpeciesReference
stoichiometry: 1.0
species: 031976

032045
type: Parameter
constant: true
value: 1.0
name: R

032022
type: Reaction
kinetic law: 524744
is version of: GO:0006889
reactant: 524684
fast: false
modifier: 524732
modifier: 524720
modifier: 524708
product: 524696
reversible: false
name: ERtoMito
is version of: GO:0006851

524684
type: SpeciesReference
stoichiometry: 1.0
species: 031990

524696
type: SpeciesReference
stoichiometry: 1.0
species: 031988

032071
type: Parameter
constant: true
value: 0.03
name: Uniport

032069
type: Parameter
constant: true
value: 0.005
name: MitNaCaEx

031998
type: Reaction
kinetic law: 524297
reactant: 524285
is version of: GO:0032961
fast: false
reversible: false
name: IP3 phosphatase: Degradation of IP3

524285
type: SpeciesReference
stoichiometry: 1.0
species: 031976

032016
type: Reaction
kinetic law: 524611
reactant: 524599
is version of: GO:0009056
fast: false
reversible: false
name: STIM/Orai degradation

524599
type: SpeciesReference
stoichiometry: 1.0
species: 031984

032043
type: Parameter
constant: true
value: 0.01
name: ERleak

032053
type: Parameter
constant: true
value: 0.02
name: STIM0

032059
type: Parameter
constant: true
value: 0.013
name: PMCA0

032033
type: Parameter
constant: true
value: 0.266
name: SERCA0

031982
type: Species
has only substance units: false
initial concentration: NaN
boundary condition: false
initial amount: 0.266
constant: false
is: SBO:0000242
name: SERCA
in compartment: 031966
is version of: P22700

032061
type: Parameter
constant: true
value: 1.0
name: kG

032018
type: Reaction
kinetic law: 524635
reactant: 524623
is version of: GO:0009056
fast: false
reversible: false
name: SERCA degradation

524623
type: SpeciesReference
stoichiometry: 1.0
species: 031982

032067
type: Parameter
constant: true
value: 0.6
name: kUnip

032002
type: Reaction
kinetic law: 524358
reactant: 524346
is version of: GO:0031587
fast: false
reversible: false
name: Recovery of IP3R from Ca2+ iinhibition when Ca2+ drops

524346
type: SpeciesReference
stoichiometry: 1.0
species: 031978

032012
type: Reaction
kinetic law: 524539
modifier: 524527
product: 524515
is version of: GO:0009058
fast: false
reversible: false
name: SERCA synthesis

524515
type: SpeciesReference
stoichiometry: 1.0
species: 031982

032051
type: Parameter
constant: true
value: 1.0
name: kSTIM

032049
type: Parameter
constant: true
value: 0.0346
name: PMleak

032020
type: Reaction
kinetic law: 524671
product: 524659
reactant: 524647
is version of: GO:0006851
fast: false
reversible: false
name: CytToMito

524659
type: SpeciesReference
stoichiometry: 1.0
species: 031988

524647
type: SpeciesReference
stoichiometry: 1.0
species: 031974

032031
type: Parameter
constant: true
value: 3.0
name: IP3R

032008
type: Reaction
kinetic law: 524479
modifier: 524467
product: 524455
is version of: GO:0009058
fast: false
reversible: false
name: PMCA synthesis

524455
type: SpeciesReference
stoichiometry: 1.0
species: 031980

031980
type: Species
boundary condition: false
name: PMCA
is version of: Q9V4C7
constant: false
is: SBO:0000242
in compartment: 031966
initial concentration: NaN
has only substance units: false
initial amount: 0.013

032004
type: Reaction
kinetic law: 524407
modifier: 524395
modifier: 524383
product: 524370
is version of: GO:0032234
fast: false
reversible: false
name: Regulation of Orai by STIM, plus leak

524370
type: SpeciesReference
stoichiometry: 1.0
species: 031974

032010
type: Reaction
kinetic law: 524503
reactant: 524491
is version of: GO:0009056
fast: false
reversible: false
name: PMCA degradation

524491
type: SpeciesReference
stoichiometry: 1.0
species: 031980

032041
type: Parameter
constant: true
value: 0.175
name: kSERCA

032047
type: Parameter
constant: true
value: 0.175
name: kIP3R

032057
type: Parameter
constant: true
value: 0.2
name: kPMCA

032037
type: Parameter
constant: true
value: 5.0
name: IP3Rinhibition

032006
type: Reaction
kinetic law: 524443
modifier: 524431
reactant: 524419
is version of: GO:0006816
fast: false
reversible: false
name: PMCA: Pumps Ca2+ across PM out of cell

524419
type: SpeciesReference
stoichiometry: 1.0
species: 031974

032065
type: Parameter
constant: true
value: 0.03
name: DirTransf

032000
type: Reaction
kinetic law: 524334
modifier: 524321
product: 524309
is version of: GO:0031586
fast: false
reversible: false
name: Inhibition of IP3R (mechanism not well understood)

524309
type: SpeciesReference
stoichiometry: 1.0
species: 031978

031994
type: Reaction
kinetic law: 524213
modifier: 524201
product: 524189
reactant: 524177
is version of: GO:0060401
fast: false
reversible: false
name: SERCA: Pumps Ca2+ into ER Ca2+ stores

524189
type: SpeciesReference
stoichiometry: 1.0
species: 031990

524177
type: SpeciesReference
stoichiometry: 1.0
species: 031974

032039
type: Parameter
constant: true
value: 0.018
name: IP3Rrecovery