delcontezerail1
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000174). Biomodels notes: 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). JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. No additional changes were made.
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Unit definitions have no effect on the numerical analysis of the model. It remains the responsibility of the modeler to ensure the internal numerical consistency of the model. If units are provided, however, the consistency of the model units will be checked.
| Name | Definition | |
|---|---|---|
| — | 1.0 second | |
| — | 1.0 mole litre^(-1.0) | |
| — | 1.0 second^(-1.0) | |
| — | 1.0 mole second^(-1.0) litre^(-1.0) | |
| — | 1.0 litre mole^(-1.0) | |
| — | 1.0 dimensionless |
| Id | Name | Spatial dimensions | Size | |
|---|---|---|---|---|
| endosome | endosomal membrane | 3.0 | 1.0 |
| Id | Name | Initial quantity | Compartment | Fixed | |
|---|---|---|---|---|---|
| R5 | Rab5-GTP | 0.001 | endosome (endosomal membrane) | ✘ | |
| R7 | Rab7-GTP | 0.001 | endosome (endosomal membrane) | ✘ | |
| r5 | Rab5-GDP | 1.0 | endosome (endosomal membrane) | ✘ | |
| r7 | Rab7-GDP | 1.0 | endosome (endosomal membrane) | ✘ |
Initial assignments are expressions that are evaluated at time=0. It is not recommended to create initial assignments for all model entities. Restrict the use of initial assignments to cases where a value is expressed in terms of values or sizes of other model entities. Note that it is not permitted to have both an initial assignment and an assignment rule for a single model entity.
| Definition |
|---|
| Id | Name | Objective coefficient | Reaction Equation and Kinetic Law | Flux bounds | |
|---|---|---|---|---|---|
| reaction_0 | recruitment of Rab5 | ∅ > r5 endosome * K1 | |||
| reaction_1 | activation of Rab5 (time) | r5 > R5 endosome * sig_act_t(r5, ke, time, kg, R5, kf) | |||
| reaction_2 | extraction of Rab5 | r5 > ∅ endosome * extraction(kminus1, r5) | |||
| reaction_3 | recruitment of Rab7 | ∅ > r7 endosome * K1 | |||
| reaction_4 | activation of Rab7 by GEF7 | r7 > R7 endosome * hill_act(r7, ke, R7, h, kg) | |||
| reaction_5 | activation of Rab7 by GEF5 | r7 > R7 endosome * sig_act(ke, r7, kg, R5, kf) | |||
| reaction_6 | hydrolysis of Rab5 by Rab7 | R5 > r5 endosome * sig_act(ke, R5, kg, R7, kf) | |||
| reaction_7 | extraction of rab7 | r7 > ∅ endosome * extraction(kminus1, r7) | |||
| reaction_8 | hydrolysis of Rab5 (intr.) | R5 > r5 endosome * hydrolysis(kh, R5) | |||
| reaction_9 | hydrolysis of Rab7 (intr.) | R7 > r7 endosome * hydrolysis(kh, R7) |
| Id | Value |
|---|
| Id | Value | Reaction | |
|---|---|---|---|
| K1 | 1.0 | reaction_0 (recruitment of Rab5) | |
| ke | 0.3 | reaction_1 (activation of Rab5 (time)) | |
| kg | 0.1 M | reaction_1 (activation of Rab5 (time)) | |
| kf | 2.5 | reaction_1 (activation of Rab5 (time)) | |
| kminus1 | 1.0 | reaction_2 (extraction of Rab5) | |
| K1 | 0.483 | reaction_3 (recruitment of Rab7) | |
| ke | 0.21 | reaction_4 (activation of Rab7 by GEF7) | |
| h | 3.0 dimensionless | reaction_4 (activation of Rab7 by GEF7) | |
| kg | 0.1 | reaction_4 (activation of Rab7 by GEF7) | |
| ke | 0.021 | reaction_5 (activation of Rab7 by GEF5) | |
| kg | 1.0 M | reaction_5 (activation of Rab7 by GEF5) | |
| kf | 3.0 | reaction_5 (activation of Rab7 by GEF5) | |
| ke | 0.31 | reaction_6 (hydrolysis of Rab5 by Rab7) | |
| kg | 0.3 M | reaction_6 (hydrolysis of Rab5 by Rab7) | |
| kf | 3.0 | reaction_6 (hydrolysis of Rab5 by Rab7) | |
| kminus1 | 0.483 | reaction_7 (extraction of rab7) | |
| kh | 0.06 | reaction_8 (hydrolysis of Rab5 (intr.)) | |
| kh | 0.15 | reaction_9 (hydrolysis of Rab7 (intr.)) |
| Definition |
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| Definition |
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| Definition |
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| Definition | |
|---|---|
| hydrolysis(kh, R) = kh * R | |
| hill_act(r, ke, R, h, kg) = r * ke * pow(R, h) / (kg + pow(R, h)) | |
| extraction(kminus1, r) = kminus1 * r | |
| sig_act_t(r, ke, t, kg, R, kf) = r * (ke * t / (100 + t)) / (1 + exp((kg - R) * kf)) | |
| sig_act(ke, r, kg, R, kf) = ke * r / (1 + exp((kg - R) * kf)) |
| Trigger | Assignments |
|---|