Lte1 promotes mitotic exit by controlling the localization of the spindle position checkpoint kinase Kin4

Falk, Jill; Chan, Lui-Heung; Amon, Angelika

doi:10.1073/pnas.1107784108

Cited by 38 publications

(46 citation statements)

References 33 publications

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“…More recent experiments revealed that Lte1, a possible Etd1 budding yeast homolog (Garcia-Cortes and McCollum 2009), rather than acting as a GEF, contributes to the proper localization of MEN regulators such as the Bfa1 GAP (Geymonat et al 2010) and the Kin4 kinase (Falk et al 2011). Given that the removal of Rga1 or Rga5 Rho1 GAPs mimics Etd1 function ( Figure 1D), we hypothesize that Etd1 binding to Rho1 ( Figure 3D and Figure 4D) may activate this GTPase by competing for binding of its negative regulators.…”

Section: Etd1 a Novel Activator Of Rho1mentioning

confidence: 99%

Feedback Regulation of SIN by Etd1 and Rho1 in Fission Yeast

et al. 2014

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In fission yeast, the septation initiation network (SIN) is thought to promote cytokinesis by downstream activation of Rho1, a conserved GTPase that controls cell growth and division. Here we show that Etd1 and PP2A-Pab1, antagonistic regulators of SIN, are Rho1 regulators. Our genetic and biochemical studies indicate that a C-terminal region of Etd1 may activate Rho1 by directly binding it, whereas an N-terminal domain confers its ability to localize at the growing tips and the division site where Rho1 functions. In opposition to Etd1, our results indicate that PP2A-Pab1 inhibits Rho1. The SIN cascade is upstream-regulated by the Spg1 GTPase. In the absence of Etd1, activity of Spg1 drops down prematurely, thereby inactivating SIN. Interestingly, we find that ectopic activation of Rho1 restores Spg1 activity in Etd1-depleted cells. By using a cytokinesis block strategy, we show that Rho1 is essential to feedbackactivate Spg1 during actomyosin ring constriction. Therefore, activation of Spg1 by Rho1, which in turn is regulated by Etd1, uncovers a novel feedback loop mechanism that ensures SIN activity while cytokinesis is progressing.F ISSION yeast cells grow by elongating at their cell ends before dividing by forming a medially placed division septum during cytokinesis. New-born cells initiate growth in a monopolar manner from the old cell end that existed before division. During G2, cells initiate growth from the new end in a process known as NETO (new end take-off). These cells then grow in a bipolar mode until mitosis, when they stop growth and initiate cell division by septation (Mitchison and Nurse 1985;Hayles and Nurse 2001). Both polar growth and septation require proper cell membrane and cell-wall synthesis to ensure cell integrity. In Schizosaccharomyces pombe, the cell wall is composed of b-glucan, a-glucan, and mannoproteins. Synthesis of the major cell wall and primary septum polymer, 1,3-b-glucan, requires the activity of Drc1/Cps1/Bgs1 1,3-b-glucan synthase, which in turn is regulated by the guanosine triphosphate (GTP)-binding protein Rho1 (Garcia et al. 2006;Cortes et al. 2007). As with all GTPases, Rho1 acts as a binary switch, cycling between inactive GDP-bound and active GTPbound conformational states (Yang et al. 2003). This transition is controlled by three types of proteins: GEFs (guanine exchange factors), which catalyze the exchange of GDP for GTP, rendering the protein active; GAPs (GTPase activating proteins), which enhance nucleotide hydrolysis, inactivating the GTPase; and guanine nucleotide dissociation inhibitors, which appear to block spontaneous activation (Garcia et al. 2006).Upon the onset of mitosis, growth ceases at the cell ends and is re-established in the middle of the cell, where the actomyosin ring forms. At the end of mitosis, once the two sets of chromosomes have segregated, actomyosin ring constriction and septum formation is triggered by the septation initiation network (SIN) from the spindle pole body (SPB) (Krapp et al. 2004;Wolfe and Gould 2005). The nucl...

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Section: Etd1 a Novel Activator Of Rho1mentioning

confidence: 99%

Feedback Regulation of SIN by Etd1 and Rho1 in Fission Yeast

et al. 2014

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“…Spindle misalignment errors that result in the retention of both SPBs in the mother cell place these two SPBs in the zone of high Kin4 activity that drives Kin4 onto both SPBs to block mitotic exit. If one SPB eventually enters the bud, Kin4 activity will be inhibited on that SPB bud by Lte1 to promote Kin4 departure and so drive MEN activation from this SPB bud (Bertazzi et al 2011;Falk et al 2011;Caydasi et al 2014). …”

Section: Extrinsic Control Of Asymmetric Spb Behavior Drives the End mentioning

confidence: 99%

The Centrosome and Its Duplication Cycle

Hagan

Glover

2015

Cold Spring Harb Perspect Biol

210

194

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“…The protein kinase Kin4 functions in opposition to Cdc5, phosphorylating Bfa1 and thus rendering the GAP insensitive to Cdc5-dependent inhibitory phosphor-ylation (Maekawa et al 2007). Tem1 is positively regulated by Lte1, which inhibits Kin4 in the bud (Bertazzi et al 2011;Falk et al 2011).…”

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confidence: 99%

Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit

Rock¹,

Amon²

2011

Genes Dev.

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In budding yeast, a Ras-like GTPase signaling cascade known as the mitotic exit network (MEN) promotes exit from mitosis. To ensure the accurate execution of mitosis, MEN activity is coordinated with other cellular events and restricted to anaphase. The MEN GTPase Tem1 has been assumed to be the central switch in MEN regulation. We show here that during an unperturbed cell cycle, restricting MEN activity to anaphase can occur in a Tem1 GTPase-independent manner. We found that the anaphase-specific activation of the MEN in the absence of Tem1 is controlled by the Polo kinase Cdc5. We further show that both Tem1 and Cdc5 are required to recruit the MEN kinase Cdc15 to spindle pole bodies, which is both necessary and sufficient to induce MEN signaling. Thus, Cdc15 functions as a coincidence detector of two essential cell cycle oscillators: the Polo kinase Cdc5 synthesis/degradation cycle and the Tem1 G-protein cycle. The Cdc15-dependent integration of these temporal (Cdc5 and Tem1 activity) and spatial (Tem1 activity) signals ensures that exit from mitosis occurs only after proper genome partitioning.

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Lte1 promotes mitotic exit by controlling the localization of the spindle position checkpoint kinase Kin4

Cited by 38 publications

References 33 publications

Feedback Regulation of SIN by Etd1 and Rho1 in Fission Yeast

Feedback Regulation of SIN by Etd1 and Rho1 in Fission Yeast

The Centrosome and Its Duplication Cycle

Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit

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