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BIOMD0000000174 - Del_Conte_Zerial2008_Rab5_Rab7_cut_out_switch

 

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Reference Publication
Publication ID: 18628746
Del Conte-Zerial P, Brusch L, Rink JC, Collinet C, Kalaidzidis Y, Zerial M, Deutsch A.
Membrane identity and GTPase cascades regulated by toggle and cut-out switches.
Mol. Syst. Biol. 2008; 4: 206
Center for Information Services and High Performance Computing, University of Technology Dresden, Dresden, Germany.  [more]
Model
Original Model: BIOMD0000000174.xml.origin
Submitter: Perla Del Conte-Zerial
Submission ID: MODEL5937037510
Submission Date: 18 Jul 2008 13:42:57 UTC
Last Modification Date: 28 Apr 2014 15:37:54 UTC
Creation Date: 28 Jul 2008 12:59:41 UTC
Encoders:  Perla Del Conte-Zerial
   Lukas Endler
set #1
bqbiol:hasTaxon Taxonomy Homo sapiens
set #2
bqbiol:isVersionOf Gene Ontology regulation of Rab GTPase activity
set #3
bqmodel:isDerivedFrom PubMed 16890441
PubMed 10591225
set #4
bqbiol:hasProperty Mathematical Modelling Ontology MAMO_0000046
Notes
Cut-out switch model

Membrane identity and GTPase cascades regulated by toggle and cut-out switches
Perla Del Conte-Zerial, Lutz Brusch, Jochen C Rink, Claudio Collinet, Yannis Kalaidzidis, Marino Zerial, and Andreas Deutsch: Molecular Systems Biology4:206 15 July 2008, doi:10.1038/msb.2008.45

This is the cut-out switch model for the Rab5 - Rab7 transition, also referred to as model 2 in the original publication.
This model is not completely described in all details in the publication. Thanks go to Barbara Szomolay and Lutz Brusch for finding and clarifying this. According to Dr. Brusch this model represents the mechanism identified by the qualitative analysis in the article in the scenario deemed most useful by the authors. For the time-course simulations it was necessary to add a time dependency to one of the parameters, which is only verbally described in the article.
As argued in the publication the switch between early and late endosomes can be triggered by a parameter change. While with fixed parameter values each switch just converges to one steady state from its initial conditions and stays there, endosomes should switch between two different states. These changes would in reality of course depend on many different factors, such as cargo composition and amount in the specific endosome, its location and some additional cellular control mechanisms and encompass many different parameters. To keep the model simple the authors chose to add a time dependency to only one reaction - ke in the activation of RAB5 is multiplied with a term monotonously increasing over time from 0 to 1. They also hard coded a time dependence in this term, 100 minutes, to make the switch occur after several hundred minutes. As long as this modulating term remains monotonic all resulting time courses should look similar, with the switching behavior depending on the initial conditions and whether the term is increasing or decreasing. Monotonic increase is a reasonable assumption for the described mechanism of cargo accumulation.
Not explicitly described in the article: activation of Rab5 (time) : r*ke*time/(100+time) /(1+e(kg-R)*kf) instead of r*ke/(1+e(kg-R)*kf)

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2009 The BioModels Team.
For more information see the terms of use.
To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Model
Publication ID: 18628746 Submission Date: 18 Jul 2008 13:42:57 UTC Last Modification Date: 28 Apr 2014 15:37:54 UTC Creation Date: 28 Jul 2008 12:59:41 UTC
Mathematical expressions
Reactions
recruitment of Rab5 activation of Rab5 (time) extraction of Rab5 recruitment of Rab7
activation of Rab7 by GEF7 activation of Rab7 by GEF5 hydrolysis of Rab5 by Rab7 extraction of rab7
hydrolysis of Rab5 (intr.) hydrolysis of Rab7 (intr.)    
Physical entities
Compartments Species
endosomal membrane Rab5-GDP Rab5-GTP Rab7-GDP
Rab7-GTP    
Reactions (10)
 
 recruitment of Rab5  → [Rab5-GDP];  
 
 activation of Rab5 (time) [Rab5-GDP] → [Rab5-GTP];   {Rab5-GTP}
 
 extraction of Rab5 [Rab5-GDP] → ;  
 
 recruitment of Rab7  → [Rab7-GDP];  
 
 activation of Rab7 by GEF7 [Rab7-GDP] → [Rab7-GTP];   {Rab7-GTP}
 
 activation of Rab7 by GEF5 [Rab7-GDP] → [Rab7-GTP];   {Rab5-GTP}
 
 hydrolysis of Rab5 by Rab7 [Rab5-GTP] → [Rab5-GDP];   {Rab7-GTP}
 
 extraction of rab7 [Rab7-GDP] → ;  
 
 hydrolysis of Rab5 (intr.) [Rab5-GTP] → [Rab5-GDP];  
 
 hydrolysis of Rab7 (intr.) [Rab7-GTP] → [Rab7-GDP];  
 
Functions (5)
 
 hydrolysis lambda(kh, R, kh*R)
 
 Sigmoid Activation lambda(ke, r, kg, R, kf, ke*r/(1+exp((kg-R)*kf)))
 
 Hills activation lambda(r, ke, R, h, kg, r*ke*R^h/(kg+R^h))
 
 extraction lambda(kminus1, r, kminus1*r)
 
 Sigmoid Activation 3 (t) lambda(r, ke, t, kg, R, kf, r*ke*t/(100+t)/(1+exp((kg-R)*kf)))
 
 endosomal membrane Spatial dimensions: 3.0  Compartment size: 1.0
 
 Rab5-GDP
Compartment: endosomal membrane
Initial concentration: 1.0
 
 Rab5-GTP
Compartment: endosomal membrane
Initial concentration: 0.0010
 
 Rab7-GDP
Compartment: endosomal membrane
Initial concentration: 1.0
 
 Rab7-GTP
Compartment: endosomal membrane
Initial concentration: 0.0010
 
recruitment of Rab5 (1)
 
   K1
Value: 1.0   (Units: Mpers)
Constant
 
activation of Rab5 (time) (3)
 
   ke
Value: 0.3   (Units: persec)
Constant
 
   kg
Value: 0.1   (Units: M)
Constant
 
   kf
Value: 2.5   (Units: lpermole)
Constant
 
extraction of Rab5 (1)
 
   kminus1
Value: 1.0   (Units: persec)
Constant
 
recruitment of Rab7 (1)
 
   K1
Value: 0.483   (Units: Mpers)
Constant
 
activation of Rab7 by GEF7 (3)
 
   ke
Value: 0.21   (Units: persec)
Constant
 
   h
Value: 3.0   (Units: dimensionless)
Constant
 
   kg
Value: 0.1
Constant
 
activation of Rab7 by GEF5 (3)
 
   ke
Value: 0.021   (Units: persec)
Constant
 
   kg
Value: 1.0   (Units: M)
Constant
 
   kf
Value: 3.0   (Units: lpermole)
Constant
 
hydrolysis of Rab5 by Rab7 (3)
 
   ke
Value: 0.31   (Units: persec)
Constant
 
   kg
Value: 0.3   (Units: M)
Constant
 
   kf
Value: 3.0   (Units: lpermole)
Constant
 
extraction of rab7 (1)
 
   kminus1
Value: 0.483   (Units: persec)
Constant
 
hydrolysis of Rab5 (intr.) (1)
 
   kh
Value: 0.06   (Units: persec)
Constant
 
hydrolysis of Rab7 (intr.) (1)
 
   kh
Value: 0.15   (Units: persec)
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000174

Curator's comment: (updated: 17 Jul 2008 13:28:14 BST)

reproduction of fig 4D from the publication the integration was performed using SBMLodeSolver (20080507)

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