scholarly journals Spindle pole bodies function as signal amplifiers in the Mitotic Exit Network

2020 ◽  
Vol 31 (9) ◽  
pp. 906-916 ◽  
Author(s):  
Ian W. Campbell ◽  
Xiaoxue Zhou ◽  
Angelika Amon
Keyword(s):  
Signal Transduction ◽  
Daughter Cell ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Mitotic Exit ◽  
Signal Transduction Cascade ◽  
Pole Body ◽  
Spindle Pole Bodies ◽  
Mitotic Exit Network ◽  
Kinase Cascade

The signal transduction cascade, known as the mitotic exit network (MEN), detects nuclear position by scaffolding its GTPase onto the spindle pole body that moves into the daughter cell during anaphase. Propagating the MEN kinase cascade onto two spindle pole bodies amplifies MEN signaling, resulting in a timely exit from mitosis.

scholarly journals Regulation of the Bfa1p–Bub2p complex at spindle pole bodies by the cell cycle phosphatase Cdc14p

2002 ◽  
Vol 157 (3) ◽  
pp. 367-379 ◽  
Author(s):  
Gislene Pereira ◽  
Claire Manson ◽  
Joan Grindlay ◽  
Elmar Schiebel
Keyword(s):  
Spindle Pole Body ◽  
Spindle Pole ◽  
Mitotic Exit ◽  
Gtpase Activating Protein ◽  
Signal Transduction Cascade ◽  
Pole Body ◽  
Spindle Pole Bodies ◽  
Short Period ◽  
Mitotic Exit Network ◽  
Early Anaphase

The budding yeast mitotic exit network (MEN) is a GTPase-driven signal transduction cascade that controls the release of the phosphatase Cdc14p from the nucleolus in anaphase and thereby drives mitotic exit. We show that Cdc14p is partially released from the nucleolus in early anaphase independent of the action of the MEN components Cdc15p, Dbf2p, and Tem1p. Upon release, Cdc14p binds to the spindle pole body (SPB) via association with the Bfa1p–Bub2p GTPase activating protein complex, which is known to regulate the activity of the G protein Tem1p. Cdc14p also interacts with this GTPase. The association of the MEN component Mob1p with the SPB acts as a marker of MEN activation. The simultaneous binding of Cdc14p and Mob1p to the SPB in early anaphase suggests that Cdc14p initially activates the MEN. In a second, later step, which coincides with mitotic exit, Cdc14p reactivates the Bfa1p–Bub2p complex by dephosphorylating Bfa1p. This inactivates the MEN and displaces Mob1p from SPBs. These data indicate that Cdc14p activates the MEN in early anaphase but later inactivates it through Bfa1p dephosphorylation and so restricts MEN activity to a short period in anaphase.

scholarly journals Inactivation of Mitotic Kinase Triggers Translocation of MEN Components to Mother-Daughter Neck in Yeast

2003 ◽  
Vol 14 (11) ◽  
pp. 4734-4743 ◽  
Author(s):  
Hong Hwa Lim ◽  
Foong May Yeong ◽  
Uttam Surana
Keyword(s):  
Chromosome Segregation ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Mitotic Exit ◽  
Mitotic Kinase ◽  
Division Site ◽  
Pole Body ◽  
Spindle Pole Bodies ◽  
Mitotic Exit Network ◽  
Mutant Cells

Chromosome segregation, mitotic exit, and cytokinesis are executed in this order during mitosis. Although a scheme coordinating sister chromatid separation and initiation of mitotic exit has been proposed, the mechanism that temporally links the onset of cytokinesis to mitotic exit is not known. Exit from mitosis is regulated by the mitotic exit network (MEN), which includes a GTPase (Tem1) and various kinases (Cdc15, Cdc5, Dbf2, and Dbf20). Here, we show that Dbf2 and Dbf20 functions are necessary for the execution of cytokinesis. Relocalization of these proteins from spindle pole bodies to mother daughter neck seems to be necessary for this role because cdc15-2 mutant cells, though capable of exiting mitosis at semipermissive temperature, are unable to localize Dbf2 (and Dbf20) to the “neck” and fail to undergo cytokinesis. These cells can assemble and constrict the actomyosin ring normally but are incapable of forming a septum, suggesting that MEN components are critical for the initiation of septum formation. Interestingly, the spindle pole body to neck translocation of Dbf2 and Dbf20 is triggered by the inactivation of mitotic kinase. The requirement of kinase inactivation for translocation of MEN components to the division site thus provides a mechanism that renders mitotic exit a prerequisite for cytokinesis.

scholarly journals Downregulation of the Tem1 GTPase by Amn1 after cytokinesis involves both nuclear import and SCF-mediated degradation

2021 ◽  
Vol 134 (19) ◽  
Author(s):  
Alain Devault ◽  
Simonetta Piatti
Keyword(s):  
Cell Cycle ◽  
Daughter Cell ◽  
Spindle Pole ◽  
Mitotic Exit ◽  
Spindle Pole Bodies ◽  
Origin Licensing ◽  
Kinase Cascade ◽  
Scf Ubiquitin Ligase ◽  
Dual Mechanism ◽  
Dependent Processes

ABSTRACT At mitotic exit the cell cycle engine is reset to allow crucial processes, such as cytokinesis and replication origin licensing, to take place before a new cell cycle begins. In budding yeast, the cell cycle clock is reset by a Hippo-like kinase cascade called the mitotic exit network (MEN), whose activation is triggered at spindle pole bodies (SPBs) by the Tem1 GTPase. Yet, MEN activity must be extinguished once MEN-dependent processes have been accomplished. One factor contributing to switching off the MEN is the Amn1 protein, which binds Tem1 and inhibits it through an unknown mechanism. Here, we show that Amn1 downregulates Tem1 through a dual mode of action. On one side, it evicts Tem1 from SPBs and escorts it into the nucleus. On the other, it promotes Tem1 degradation as part of a Skp, Cullin and F-box-containing (SCF) ubiquitin ligase. Tem1 inhibition by Amn1 takes place after cytokinesis in the bud-derived daughter cell, consistent with its asymmetric appearance in the daughter cell versus the mother cell. This dual mechanism of Tem1 inhibition by Amn1 may contribute to the rapid extinguishing of MEN activity once it has fulfilled its functions.

scholarly journals Mutual regulation of cyclin-dependent kinase and the mitotic exit network

2010 ◽  
Vol 188 (3) ◽  
pp. 351-368 ◽  
Author(s):  
Cornelia König ◽  
Hiromi Maekawa ◽  
Elmar Schiebel
Keyword(s):  
Spindle Pole Body ◽  
Spindle Pole ◽  
Mitotic Exit ◽  
Cyclin Dependent Kinase ◽  
Spatial Regulation ◽  
Daughter Cells ◽  
Pole Body ◽  
Mitotic Exit Network ◽  
Mutual Regulation ◽  
Early Anaphase

The mitotic exit network (MEN) is a spindle pole body (SPB)–associated, GTPase-driven signaling cascade that controls mitotic exit. The inhibitory Bfa1–Bub2 GTPase-activating protein (GAP) only associates with the daughter SPB (dSPB), raising the question as to how the MEN is regulated on the mother SPB (mSPB). Here, we show mutual regulation of cyclin-dependent kinase 1 (Cdk1) and the MEN. In early anaphase Cdk1 becomes recruited to the mSPB depending on the activity of the MEN kinase Cdc15. Conversely, Cdk1 negatively regulates binding of Cdc15 to the mSPB. In addition, Cdk1 phosphorylates the Mob1 protein to inhibit the activity of Dbf2–Mob1 kinase that regulates Cdc14 phosphatase. Our data revise the understanding of the spatial regulation of the MEN. Although MEN activity in the daughter cells is controlled by Bfa1–Bub2, Cdk1 inhibits MEN activity at the mSPB. Consistent with this model, only triple mutants that lack BUB2 and the Cdk1 phosphorylation sites in Mob1 and Cdc15 show mitotic exit defects.

scholarly journals The Mitotic Exit Network Regulates Spindle Pole Body Selection During Sporulation ofSaccharomyces cerevisiae

Genetics ◽  
2017 ◽  
Vol 206 (2) ◽  
pp. 919-937 ◽  
Author(s):  
Christian Renicke ◽  
Ann-Katrin Allmann ◽  
Anne Pia Lutz ◽  
Thomas Heimerl ◽  
Christof Taxis
Keyword(s):  
Spindle Pole Body ◽  
Spindle Pole ◽  
Mitotic Exit ◽  
Pole Body ◽  
Mitotic Exit Network

scholarly journals Cdk1 promotes cytokinesis in fission yeast through activation of the septation initiation network

2014 ◽  
Vol 25 (15) ◽  
pp. 2250-2259 ◽  
Author(s):  
Nicole Rachfall ◽  
Alyssa E. Johnson ◽  
Sapna Mehta ◽  
Jun-Song Chen ◽  
Kathleen L. Gould
Keyword(s):  
Cell Cycle ◽  
Spindle Pole Body ◽  
Complete Removal ◽  
Spindle Pole ◽  
Cyclin Dependent Kinase ◽  
Gtpase Activating Protein ◽  
Pole Body ◽  
Kinase Cascade ◽  
Septation Initiation Network ◽  
Cycle Dependent

In Schizosaccharomyces pombe, late mitotic events are coordinated with cytokinesis by the septation initiation network (SIN), an essential spindle pole body (SPB)–associated kinase cascade, which controls the formation, maintenance, and constriction of the cytokinetic ring. It is not fully understood how SIN initiation is temporally regulated, but it depends on the activation of the GTPase Spg1, which is inhibited during interphase by the essential bipartite GTPase-activating protein Byr4-Cdc16. Cells are particularly sensitive to the modulation of Byr4, which undergoes cell cycle–dependent phosphorylation presumed to regulate its function. Polo-like kinase, which promotes SIN activation, is partially responsible for Byr4 phosphorylation. Here we show that Byr4 is also controlled by cyclin-dependent kinase (Cdk1)–mediated phosphorylation. A Cdk1 nonphosphorylatable Byr4 phosphomutant displays severe cell division defects, including the formation of elongated, multinucleate cells, failure to maintain the cytokinetic ring, and compromised SPB association of the SIN kinase Cdc7. Our analyses show that Cdk1-mediated phosphoregulation of Byr4 facilitates complete removal of Byr4 from metaphase SPBs in concert with Plo1, revealing an unexpected role for Cdk1 in promoting cytokinesis through activation of the SIN pathway.

scholarly journals Spatial signals link exit from mitosis to spindle position

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Jill Elaine Falk ◽  
Dai Tsuchiya ◽  
Jolien Verdaasdonk ◽  
Soni Lacefield ◽  
Kerry Bloom ◽  
...  
Keyword(s):  
Spindle Pole ◽  
Mitotic Exit ◽  
Zone Model ◽  
Cytoplasmic Microtubule ◽  
Binucleate Cells ◽  
Spindle Pole Bodies ◽  
Mitotic Exit Network ◽  
Bud Neck ◽  
Competing Models ◽  
Spindle Position

In budding yeast, if the spindle becomes mispositioned, cells prevent exit from mitosis by inhibiting the mitotic exit network (MEN). The MEN is a signaling cascade that localizes to spindle pole bodies (SPBs) and activates the phosphatase Cdc14. There are two competing models that explain MEN regulation by spindle position. In the 'zone model', exit from mitosis occurs when a MEN-bearing SPB enters the bud. The 'cMT-bud neck model' posits that cytoplasmic microtubule (cMT)-bud neck interactions prevent MEN activity. Here we find that 1) eliminating cMT– bud neck interactions does not trigger exit from mitosis and 2) loss of these interactions does not precede Cdc14 activation. Furthermore, using binucleate cells, we show that exit from mitosis occurs when one SPB enters the bud despite the presence of a mispositioned spindle. We conclude that exit from mitosis is triggered by a correctly positioned spindle rather than inhibited by improper spindle position.

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