title: Tem1 localization to the spindle pole bodies is essential for mitotic exit and impairs spindle checkpoint function.
abstract: The mitotic exit network (MEN) is a signaling cascade that triggers inactivation of the mitotic cyclin-dependent kinases and exit from mitosis. The GTPase Tem1 localizes on the spindle pole bodies (SPBs) and initiates MEN signaling. Tem1 activity is inhibited until anaphase by Bfa1-Bub2. These proteins are also part of the spindle position checkpoint (SPOC), a surveillance mechanism that restrains mitotic exit until the spindle is correctly positioned. Here, we show that regulation of Tem1 localization is essential for the proper function of the MEN and the SPOC. We demonstrate that the dynamics of Tem1 loading onto SPBs determine the recruitment of other MEN components to this structure, and reevaluate the interdependence in the localization of Tem1, Bfa1, and Bub2. We also find that removal of Tem1 from the SPBs is critical for the SPOC to impede cell cycle progression. Finally, we demonstrate for the first time that localization of Tem1 to the SPBs is a requirement for mitotic exit.
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla, Sevilla, Spain.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Valerio-Santiago
authors.forename: Fernando
authors.initials: F
authors.lastname: Monje-Casas
mesh_terms: D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D008938:Mitosis / Q000502:physiology*; D020559:Monomeric GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: C119117:BFA1 protein, S cerevisiae; D003598:Cytoskeletal Proteins; D029701:Saccharomyces cerevisiae Proteins; C089965:TEM1 protein, S cerevisiae; D020559:Monomeric GTP-Binding Proteins