Caydasi2012 - Regulation of Tem1 by the GAP complex in Spindle Position Checkpoint - Ubiquitous inactive model

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Model Identifier
BIOMD0000000702
Short description
Regulation of Tem1 by the GAP complex in Spindle Position Checkpoint - Ubiquitous inactive

This model is described in the article:

Caydasi AK, Lohel M, GrĂ¼nert G, Dittrich P, Pereira G, Ibrahim B.
Mol. Syst. Biol. 2012; 8: 582

Abstract:

The orientation of the mitotic spindle with respect to the polarity axis is crucial for the accuracy of asymmetric cell division. In budding yeast, a surveillance mechanism called the spindle position checkpoint (SPOC) prevents exit from mitosis when the mitotic spindle fails to align along the mother-to-daughter polarity axis. SPOC arrest relies upon inhibition of the GTPase Tem1 by the GTPase-activating protein (GAP) complex Bfa1-Bub2. Importantly, reactions signaling mitotic exit take place at yeast centrosomes (named spindle pole bodies, SPBs) and the GAP complex also promotes SPB localization of Tem1. Yet, whether the regulation of Tem1 by Bfa1-Bub2 takes place only at the SPBs remains elusive. Here, we present a quantitative analysis of Bfa1-Bub2 and Tem1 localization at the SPBs. Based on the measured SPB-bound protein levels, we introduce a dynamical model of the SPOC that describes the regulation of Bfa1 and Tem1. Our model suggests that Bfa1 interacts with Tem1 in the cytoplasm as well as at the SPBs to provide efficient Tem1 inhibition.

This model is hosted on BioModels Database and identified by: BIOMD0000000702.

To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8.

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Format
SBML (L2V4)
Related Publication
  • A dynamical model of the spindle position checkpoint.
  • Caydasi AK, Lohel M, GrĂ¼nert G, Dittrich P, Pereira G, Ibrahim B
  • Molecular Systems Biology , 1/ 2012 , Volume 8 , pages: 582 , PubMed ID: 22580890
  • Molecular Biology of Centrosomes and Cilia, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany.
  • The orientation of the mitotic spindle with respect to the polarity axis is crucial for the accuracy of asymmetric cell division. In budding yeast, a surveillance mechanism called the spindle position checkpoint (SPOC) prevents exit from mitosis when the mitotic spindle fails to align along the mother-to-daughter polarity axis. SPOC arrest relies upon inhibition of the GTPase Tem1 by the GTPase-activating protein (GAP) complex Bfa1-Bub2. Importantly, reactions signaling mitotic exit take place at yeast centrosomes (named spindle pole bodies, SPBs) and the GAP complex also promotes SPB localization of Tem1. Yet, whether the regulation of Tem1 by Bfa1-Bub2 takes place only at the SPBs remains elusive. Here, we present a quantitative analysis of Bfa1-Bub2 and Tem1 localization at the SPBs. Based on the measured SPB-bound protein levels, we introduce a dynamical model of the SPOC that describes the regulation of Bfa1 and Tem1. Our model suggests that Bfa1 interacts with Tem1 in the cytoplasm as well as at the SPBs to provide efficient Tem1 inhibition.
Contributors
Submitter of the first revision: Bashar Ibrahim
Submitter of this revision: Rahuman Sheriff
Modellers: Rahuman Sheriff, Bashar Ibrahim

Metadata information

is (2 statements)
BioModels Database MODEL1202090003
BioModels Database BIOMD0000000702

isDescribedBy (2 statements)
hasTaxon (1 statement)
hasProperty (4 statements)

Curation status
Curated


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Model files

BIOMD0000000702_url.xml SBML L2V4 representation of Caydasi2012 - Regulation of Tem1 by the GAP complex in Spindle Position Checkpoint - Ubiquitous inactive model 242.79 KB Preview | Download

Additional files

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BIOMD0000000702.xpp Auto-generated XPP file 24.51 KB Preview | Download
BIOMD0000000702_urn.xml Auto-generated SBML file with URNs 241.64 KB Preview | Download
MODEL1202090003_Fig5 iii.cps The attached COPASI file reproduces Figure 5(iii) of the reference publication. 294.01 KB Preview | Download
MODEL1202090003_Fig5 iii.sedml SEDML file to reproduce Figure 5(iii) in the reference publication. 6.78 KB Preview | Download

  • Model originally submitted by : Bashar Ibrahim
  • Submitted: Feb 9, 2012 7:15:02 PM
  • Last Modified: May 22, 2018 12:21:23 PM
Revisions
  • Version: 3 public model Download this version
    • Submitted on: May 22, 2018 12:21:23 PM
    • Submitted by: Rahuman Sheriff
    • With comment: Model name updated using online editor.
  • Version: 2 public model Download this version
    • Submitted on: May 10, 2012 2:51:07 PM
    • Submitted by: Bashar Ibrahim
    • With comment: Current version of Caydasi2012_SPOC_UbiquitousInactive
  • Version: 1 public model Download this version
    • Submitted on: Feb 9, 2012 7:15:02 PM
    • Submitted by: Bashar Ibrahim
    • With comment: Original import of MODEL1202090003.xml.origin

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
Bfa1

Mitotic check point protein BFA1
2.03E-8 mol
Tem1GTP

GTP ; Protein TEM1
4.91E-8 mol
Bfa1 Tem1GDP

Protein TEM1 ; GDP ; Mitotic check point protein BFA1
0.0 mol
Bfa1P5 Tem1GDP

Mitotic check point protein BFA1 ; increased phosphorylation ; Protein TEM1 ; GDP
0.0 mol
SPB B

urn:miriam:sbo:SBO%3A0000494
8.33E-5 mol
Tem1GDP

Protein TEM1 ; GDP
7.99E-9 mol
Reactions
Reactions Rate Parameters
SPB_B + Bfa1 => B_Bfa1 c3*(konB*SPB_B*Bfa1-koffB*B_Bfa1) konB = 1250000.0 l/(mol*s); koffB = 0.0012 1/s
Tem1GTP + B_Bfa1P4 => B_Bfa1P4_Tem1GTP c3*(konB4T*B_Bfa1P4*Tem1GTP-koffBT*B_Bfa1P4_Tem1GTP) konB4T = 3.65E7 l/(mol*s); koffBT = 0.183 1/s
Bfa1P4 + Tem1GTP => Bfa1P4_Tem1GTP c2*(alpha*konB4T*Bfa1P4*Tem1GTP-koffBT*Bfa1P4_Tem1GTP) konB4T = 3.65E7 l/(mol*s); alpha = 1.0 1; koffBT = 0.183 1/s
Bfa1P4_Tem1GDP => Bfa1_Tem1GDP c2*krKin4*Bfa1P4_Tem1GDP krKin4 = 0.0251 1/s
Bfa1P5_Tem1GDP => Bfa1_Tem1GDP c2*u*krCdc5*Bfa1P5_Tem1GDP krCdc5 = 0.01 1/s; u = 1.0 1
Bfa1P4_Tem1GTP + SPB_B => B_Bfa1P4_Tem1GTP c3*(konB4*Bfa1P4_Tem1GTP*SPB_B-koffB4*B_Bfa1P4_Tem1GTP) koffB4 = 0.0365 1/s; konB4 = 20000.0 l/(mol*s)
Bfa1 => Bfa1P4 c2*u*kfKin4Cyto*Bfa1 kfKin4Cyto = 0.09 1/s; u = 1.0 1
Bfa1 + Tem1GTP => Bfa1_Tem1GTP c2*(alpha*konBT*Bfa1*Tem1GTP-koffBT*Bfa1_Tem1GTP) alpha = 1.0 1; koffBT = 0.183 1/s; konBT = 3.65E7 l/(mol*s)
Tem1GTP + SPB_T => T_Tem1GTP c3*(konT*SPB_T*Tem1GTP-koffT*T_Tem1GTP) konT = 1900000.0 l/(mol*s); koffT = 0.183 1/s
Bfa1P5 + Tem1GDP => Bfa1P5_Tem1GDP c2*(alpha*konB5T*Bfa1P5*Tem1GDP-koffBT*Bfa1P5_Tem1GDP) alpha = 1.0 1; koffBT = 0.183 1/s; konB5T = 7000000.0 l/(mol*s)
Curator's comment:
(added: 21 May 2018, 16:41:53, updated: 21 May 2018, 16:41:53)
Figure 5(iii) of the reference publication was reproduced was using COPASI 4.23 built 184. The following initial conditions were corrected (1) B-Bfa1P5 set to 0 (to fix a typo in publication) (2) B-Bfa1 set to 8.3e-5 (to fix a typo in publication) and (3) B-Bfa1-Tem1P5GTP set to 5e-6 ( to match the reference figure)