A dynamical model of the spindle position checkpoint

Ayse Koca Caydasi; Maiko Lohel; Gerd Grünert; Peter Dittrich; Gislene Pereira; Bashar Ibrahim

doi:10.1038/msb.2012.15

A dynamical model of the spindle position checkpoint

Mol Syst Biol. 2012 May 8:8:582. doi: 10.1038/msb.2012.15.

Authors

Ayse Koca Caydasi¹, Maiko Lohel, Gerd Grünert, Peter Dittrich, Gislene Pereira, Bashar Ibrahim

Affiliation

¹ Molecular Biology of Centrosomes and Cilia, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Asymmetric Cell Division
Cell Cycle
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Computer Simulation
Cytoplasm / genetics
Cytoskeletal Proteins / genetics
Cytoskeletal Proteins / metabolism
GTP Phosphohydrolases / antagonists & inhibitors
GTP Phosphohydrolases / metabolism
GTPase-Activating Proteins / genetics
GTPase-Activating Proteins / metabolism
Gene Expression Regulation, Fungal*
Microscopy, Fluorescence
Mitosis
Models, Theoretical*
Monomeric GTP-Binding Proteins / antagonists & inhibitors
Monomeric GTP-Binding Proteins / genetics
Saccharomyces cerevisiae / genetics*
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / antagonists & inhibitors
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism
Spindle Apparatus / genetics
Spindle Apparatus / metabolism*
Systems Biology / methods*

Substances

BFA1 protein, S cerevisiae
BUB2 protein, S cerevisiae
Cell Cycle Proteins
Cytoskeletal Proteins
GTPase-Activating Proteins
Saccharomyces cerevisiae Proteins
TEM1 protein, S cerevisiae
GTP Phosphohydrolases
Monomeric GTP-Binding Proteins