title: A dynamical model of the spindle position checkpoint.
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.
authors.affiliation: Molecular Biology of Centrosomes and Cilia, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany.
authors.forename: Ayse Koca
authors.initials: AK
authors.lastname: Caydasi
authors.forename: Maiko
authors.initials: M
authors.lastname: Lohel
authors.forename: Gerd
authors.initials: G
authors.lastname: Grünert
authors.forename: Peter
authors.initials: P
authors.lastname: Dittrich
authors.forename: Gislene
authors.initials: G
authors.lastname: Pereira
authors.forename: Bashar
authors.initials: B
authors.lastname: Ibrahim
mesh_terms: D060049:Asymmetric Cell Division; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D003198:Computer Simulation; D003593:Cytoplasm / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D008856:Microscopy, Fluorescence; D008938:Mitosis; D008962:Models, Theoretical; D020559:Monomeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D049490:Systems Biology / Q000379:methods*
chemical_list: C119117:BFA1 protein, S cerevisiae; C070351:BUB2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D029701:Saccharomyces cerevisiae Proteins; C089965:TEM1 protein, S cerevisiae; D020558:GTP Phosphohydrolases; D020559:Monomeric GTP-Binding Proteins