Caydasi2012 - Inhibition of Tem1 by the GAP complex in Spindle Position Checkpoint
This model is from the article:
A dynamical model of the spindle position checkpoint
Ayse Koca Caydasi, Maiko Lohel, Gerd Grünert, Peter Dittrich, Gislene Pereira, Bashar Ibrahim Molecular Systems Biology
2012; 582
doi: 10.1038/msb.2012.15
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.
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A dynamical model of the spindle position checkpoint.
- Caydasi AK, Lohel M, Grünert 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.
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Bashar Ibrahim, Krishna Kumar Tiwari
Metadata information
hasTaxon (1 statement)
hasProperty (4 statements)
Gene Ontology regulation of cell cycle
Gene Ontology mitotic spindle orientation checkpoint
Gene Ontology mitotic spindle organization
isDescribedBy (1 statement)
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
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| MODEL1202090001_FINAL.xml | SBML L2V4 representation of Caydasi2012_SPOC_HotSpotAssociation | 251.10 KB | Preview | Download |
Additional files |
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| MODEL1202090001-biopax2.owl | Auto-generated BioPAX (Level 2) | 54.17 KB | Preview | Download |
| MODEL1202090001-biopax3.owl | Auto-generated BioPAX (Level 3) | 103.49 KB | Preview | Download |
| MODEL1202090001.m | Auto-generated Octave file | 18.47 KB | Preview | Download |
| MODEL1202090001.pdf | Auto-generated PDF file | 237.91 KB | Preview | Download |
| MODEL1202090001.png | Auto-generated Reaction graph (PNG) | 496.88 KB | Preview | Download |
| MODEL1202090001.sci | Auto-generated Scilab file | 67.00 Bytes | Preview | Download |
| MODEL1202090001.svg | Auto-generated Reaction graph (SVG) | 93.42 KB | Preview | Download |
| MODEL1202090001.vcml | Auto-generated VCML file | 87.69 KB | Preview | Download |
| MODEL1202090001.xpp | Auto-generated XPP file | 15.07 KB | Preview | Download |
| MODEL1202090001_FINAL.cps | COPASI 4.28 (Build217) file for the model | 318.08 KB | Preview | Download |
| MODEL1202090001_FINAL.sedml | SEDML file for the model | 6.75 KB | Preview | Download |
| MODEL1202090001_url.xml | Original file submitted by author | 57.03 KB | Preview | Download |
| MODEL1202090001_urn.xml | Auto-generated SBML file with URNs | 63.72 KB | Preview | Download |
- Model originally submitted by : Bashar Ibrahim
- Submitted: Feb 9, 2012 7:12:36 PM
- Last Modified: Jul 14, 2020 12:46:27 PM
Revisions
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Version: 4
- Submitted on: Jul 14, 2020 12:46:27 PM
- Submitted by: Krishna Kumar Tiwari
- With comment: Reupdated model for publication related requirement from developers
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Version: 3
- Submitted on: Jul 14, 2020 12:26:01 PM
- Submitted by: Krishna Kumar Tiwari
- With comment: Updated model file recovered from Matthiew work
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Version: 2
- Submitted on: May 10, 2012 2:48:51 PM
- Submitted by: Bashar Ibrahim
- With comment: Current version of Caydasi2012_SPOC_HotSpotAssociation
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Version: 1
- Submitted on: Feb 9, 2012 7:12:36 PM
- Submitted by: Bashar Ibrahim
- With comment: Original import of MODEL1202090001.xml.origin
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: Variable used inside SBML models
| Species | Initial Concentration/Amount |
|---|---|
| Tem1GDP Protein TEM1 ; GDP |
7.99E-9 mol |
| Bfa1 Tem1GDP Mitotic check point protein BFA1 ; Protein TEM1 ; GDP |
0.0 mol |
| Inactive Bfa1 at the SPB Mitotic check point protein BFA1 ; inactive |
150.493316085 mol |
| SPB B binding site |
8.33E-5 mol |
| SPB T binding site |
1.66E-4 mol |
| B Bfa1 Tem1GTP binding site ; Mitotic check point protein BFA1 ; GTP ; Protein TEM1 |
0.0 mol |
| B Bfa1 Tem1GDP Mitotic check point protein BFA1 ; Protein TEM1 ; binding site ; GDP |
0.0 mol |
| Bfa1 Tem1GTP Mitotic check point protein BFA1 ; Protein TEM1 ; GTP |
0.0 mol |
| Reactions | Rate | Parameters |
|---|---|---|
| Bfa1 + Tem1GDP => Bfa1_Tem1GDP | c2*(alpha*konBT*Bfa1*Tem1GDP-koffBT*Bfa1_Tem1GDP) | alpha = 1.0 1; koffBT = 0.183 1/s; konBT = 3.65E7 l/(mol*s) |
| Inactive_Bfa1_at_the_SPB = ((1-q)*(B_Bfa1+B_Bfa1_Tem1GTP+B_Bfa1_Tem1GDP)+B_Bfa1P5+B_Bfa1P5_Tem1GTP+B_Bfa1P5_Tem1GDP)*c3*avogadro | [] | avogadro = 6.0221415E23; q = 0.0 1 |
| Bfa1P4 + SPB_B => B_Bfa1P4 | c3*(konB4*SPB_B*Bfa1P4-koffB4*B_Bfa1P4) | koffB4 = 0.0365 1/s; konB4 = 20000.0 l/(mol*s) |
| Tem1GDP + SPB_T => T_Tem1GDP | c3*(konT*SPB_T*Tem1GDP-koffT*T_Tem1GDP) | konT = 1900000.0 l/(mol*s); koffT = 0.183 1/s |
| Tem1GDP + B_Bfa1P4 => B_Bfa1P4_Tem1GDP | c3*(konB4T*B_Bfa1P4*Tem1GDP-koffBT*B_Bfa1P4_Tem1GDP) | konB4T = 3.65E7 l/(mol*s); koffBT = 0.183 1/s |
| B_Bfa1_Tem1GTP => B_Bfa1_Tem1GDP | c3*khydBT*B_Bfa1_Tem1GTP | khydBT = 0.00224 1/s |
| Tem1GDP + B_Bfa1 => B_Bfa1_Tem1GDP | c3*(konBT*B_Bfa1*Tem1GDP-koffBT*B_Bfa1_Tem1GDP) | koffBT = 0.183 1/s; konBT = 3.65E7 l/(mol*s) |
| Bfa1_Tem1GTP => Bfa1P4_Tem1GTP | c2*u*kfKin4Cyto*Bfa1_Tem1GTP | kfKin4Cyto = 0.09 1/s; u = 1.0 1 |
| Tem1GTP + SPB_T => T_Tem1GTP | c3*(konT*SPB_T*Tem1GTP-koffT*T_Tem1GTP) | konT = 1900000.0 l/(mol*s); koffT = 0.183 1/s |
(added: 14 Jul 2020, 12:27:43, updated: 14 Jul 2020, 12:27:43)