Phosphorylation of Lte1 by Cdk prevents polarized growth during mitotic arrest in <i>S. cerevisiae</i>

Geymonat, Marco; Spanos, Adonis; Jensen, Sanne; Sedgwick, Steven G.

doi:10.1083/jcb.201005070

Cited by 23 publications

(34 citation statements)

References 57 publications

(124 reference statements)

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“…Mutations that allow cells to reorient their polarity axis without grossly affecting the structure of the septins demonstrate that a septin ring is not the only and probably not the major factor for keeping the polarity axis during the later stages of the cell cycle. For example, certain mitotic arrest mutations of LTE1 induce the growth of buds that is orthogonal to the original axis and that will eventually lead to a characteristic hammerhead morphology (Geymonat et al, 2010). These and other experiments seem to indicate the presence of multiple pathways that are either used simultaneously or at different periods of the cell cycle to guarantee the observed robustness in determining the morphology of the yeast.…”

Section: Discussionmentioning

confidence: 99%

Septin rings act as template for myosin higher-order structures and inhibit redundant polarity establishment

Schneider

Grois

Renz

et al. 2013

Journal of Cell Science

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SummaryThe mechanisms of the coordinated assembly and disassembly of the septin/myosin ring is central for the understanding of polar growth and cytokinesis in yeast and other organisms. The septin-and myosin-binding protein Bni5p provides a dual function during the formation and disassembly of septin/myosin rings. Early in the cell cycle, Bni5p captures Myo1p at the incipient bud site and actively transforms it into higher-order structures. Additionally, Bni5p stabilizes the septin/myosin ring and is released from the septins shortly before the onset of cytokinesis. If this Bni5p dissociation from the septins is artificially prevented, ring disassembly is impaired and the untimely appearance of septin/myosin ring is induced. The prematurely formed septin/myosin rings delay the establishment of a new polarity axis and the progression into a new cell cycle. This observation suggests a negative feedback between septin/myosin ring formation and polarity establishment that might help to guarantee the singular assembly of this structure and the synchronization of its formation with the cell cycle.

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Section: Discussionmentioning

confidence: 99%

Septin rings act as template for myosin higher-order structures and inhibit redundant polarity establishment

Schneider

Grois

Renz

et al. 2013

Journal of Cell Science

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“…The relationship between mitotic CDK and polar growth is well known in S. cerevisiae, where Cdc28 associated to Clb cyclins inhibits apical growth and triggers isotropic bud growth (Lew and Reed, 1993). Recent work showed that this inhibition involves the Cdc28-Clb-dependent phosphorylation of Lte1, which in turn act in a hitherto unknown process that prevents untimely-polarized growth by interfering with the activity of small GTPases Ras and Bud1 during G2/M (Geymonat et al, 2010). Although this kind of explanation could be also applied to U. maydis, it is likely that more than one element could be involved in the connections between cell cycle regulation and polar growth.…”

Section: Discussionmentioning

confidence: 99%

The distinct wiring between cell cycle regulation and the widely conserved Morphogenesis-Related (MOR) pathway in the fungus Ustilago maydis determines the morphological outcome

Sartorel

Pérez-Martı́n

2012

Journal of Cell Science

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SummaryThe morphogenesis-related NDR kinase (MOR) pathway regulates morphogenesis in fungi. In spite of the high conservation of its components, impairing their functions results in highly divergent cellular responses depending on the fungal species. The reasons for such differences are unclear. Here we propose that the species-specific connections between cell cycle regulation and the MOR pathway could be partly responsible for these divergences. We based our conclusion on the characterization of the MOR pathway in the fungus Ustilago maydis. Each gene that encodes proteins of this pathway in U. maydis was deleted. All mutants exhibited a constitutive hyperpolarized growth, contrasting with the loss of polarity observed in other fungi. Using a conditional allele of the central NDR kinase Ukc1, we found that impairing MOR function resulted in a prolonged G2 phase. This cell cycle delay appears to be the consequence of an increase in Cdk1 inhibitory phosphorylation. Strikingly, prevention of the inhibitory Cdk1 phosphorylation abolished the hyperpolarized growth associated with MOR pathway depletion. We found that the prolonged G2 phase resulted in higher levels of expression of crk1, a conserved kinase that promotes polar growth in U. maydis. Deletion of crk1 also abolished the dramatic activation of polar growth in cells lacking the MOR pathway. Taken together, our results suggest that Cdk1 inhibitory phosphorylation may act as an integrator of signaling cascades regulating fungal morphogenesis and that the distinct morphological response observed in U. maydis upon impairment of the MOR pathway could be due to a cell cycle deregulation.

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“…Different GTPases may have common regulators to coordinate their functions. Lte1 is known to regulate Tem 1 GTPase at the SPB (Geymonat et al 2010) and the small GTPases Ras and Bud1 at the cell cortex, a dual function that allows Lte1 to couple mitotic progression and morphological development in budding yeast (Geymonat et al 2010). Thus, in addition to the feedback-loop mechanism proposed here, a parallel function of Etd1 in Spg1 and Rho1 regulation would help to coordinate ring constriction and SIN (Figure 8).…”

Section: Coordination Between Sin and Cytokinesismentioning

confidence: 99%

“…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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Phosphorylation of Lte1 by Cdk prevents polarized growth during mitotic arrest in S. cerevisiae

Abstract: Lte1 interacts with and inhibits the small GTPases Ras and Bud1, blocking polarization until mitosis is complete.

Cited by 23 publications

References 57 publications

Septin rings act as template for myosin higher-order structures and inhibit redundant polarity establishment

Septin rings act as template for myosin higher-order structures and inhibit redundant polarity establishment

The distinct wiring between cell cycle regulation and the widely conserved Morphogenesis-Related (MOR) pathway in the fungus Ustilago maydis determines the morphological outcome

Feedback Regulation of SIN by Etd1 and Rho1 in Fission Yeast

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