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A novel function of Saccharomyces cerevisiae CDC5 in cytokinesis.

Song S, Lee KS - J. Cell Biol. (2001)

Bottom Line: Overexpression of the COOH-terminal domain of Cdc5 (cdc5DeltaN), but not the corresponding polo-box mutant, resulted in connected cells.The polo-box-dependent interactions between Cdc5 and septins (Cdc11 and Cdc12) and genetic interactions between the dominant-negative cdc5DeltaN and Cyk2/Hof1 or Myo1 suggest that direct interactions between cdc5DeltaN and septins resulted in inhibition of Cyk2/Hof1- and Myo1-mediated cytokinetic pathways.Thus, we propose that Cdc5 may coordinate mitotic exit with cytokinesis by participating in both anaphase promoting complex activation and a polo-box-dependent cytokinetic pathway.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Metabolism, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

ABSTRACT
Coordination of mitotic exit with timely initiation of cytokinesis is critical to ensure completion of mitotic events before cell division. The Saccharomyces cerevisiae polo kinase Cdc5 functions in a pathway leading to the degradation of mitotic cyclin Clb2, thereby permitting mitotic exit. Here we provide evidence that Cdc5 also plays a role in regulating cytokinesis and that an intact polo-box, a conserved motif in the noncatalytic COOH-terminal domain of Cdc5, is required for this event. Depletion of Cdc5 function leads to an arrest in cytokinesis. Overexpression of the COOH-terminal domain of Cdc5 (cdc5DeltaN), but not the corresponding polo-box mutant, resulted in connected cells. These cells shared cytoplasms with incomplete septa, and possessed aberrant septin ring structures. Provision of additional copies of endogenous CDC5 remedied this phenotype, suggesting a dominant-negative inhibition of cytokinesis. The polo-box-dependent interactions between Cdc5 and septins (Cdc11 and Cdc12) and genetic interactions between the dominant-negative cdc5DeltaN and Cyk2/Hof1 or Myo1 suggest that direct interactions between cdc5DeltaN and septins resulted in inhibition of Cyk2/Hof1- and Myo1-mediated cytokinetic pathways. Thus, we propose that Cdc5 may coordinate mitotic exit with cytokinesis by participating in both anaphase promoting complex activation and a polo-box-dependent cytokinetic pathway.

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Model proposing the role of Cdc5 in coordinating the mitotic exit pathway and cytokinesis. At late anaphase/telophase, but before full spindle elongation and assembly of contractile ring, Cdc5 carries out two important functions. First, in a polo-box–independent manner, Cdc5 activates APC, which leads to inactivation of Cdc28/Clb2, thereby permitting mitotic exit. Second, in a polo-box–dependent manner, Cdc5 localizes at cytokinetic neck filaments and promotes the cytokinetic functions of septins.
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Figure 8: Model proposing the role of Cdc5 in coordinating the mitotic exit pathway and cytokinesis. At late anaphase/telophase, but before full spindle elongation and assembly of contractile ring, Cdc5 carries out two important functions. First, in a polo-box–independent manner, Cdc5 activates APC, which leads to inactivation of Cdc28/Clb2, thereby permitting mitotic exit. Second, in a polo-box–dependent manner, Cdc5 localizes at cytokinetic neck filaments and promotes the cytokinetic functions of septins.

Mentions: Our data suggest that Cdc5 plays dual roles in a late stage of M phase. We propose that, in addition to activation of APC, Cdc5 activity is required for proper function of septin ring structures during cytokinesis (Fig. 8). In this scenario, during or shortly after activation of APC, a fraction of Cdc5 relocalizes to bud-neck to carry out its cytokinetic function, an event that requires an intact polo-box. A dominant-negative cdc5ΔN, which localizes at the neck-filament, does not interfere with APC activation and mitotic exit pathway. However, it inhibits Cdc5 localization at the neck filaments, thereby impairing septin functions critical for cytokinesis. Our model also helps explain the phenotypes associated with overexpression of Cdc5 (Song et al. 2000) or an activated form of Plk (Lee et al. 1999). In both cases, unregulated Cdc5/Plk activity may have induced abnormally elongated buds by activation of APC, whereas ectopic septin rings may have arisen by reinforcing septin ring organization. Our data suggest that activation of the APC does not require a polo-box–dependent localization of Cdc5 at the septin rings, whereas overexpression of the polo-box domain is sufficient to inhibit cytokinesis. Thus, temporal and spatial regulation of Cdc5 may provide an important mechanism to coordinate mitotic exit pathway with initiation of cytokinesis.


A novel function of Saccharomyces cerevisiae CDC5 in cytokinesis.

Song S, Lee KS - J. Cell Biol. (2001)

Model proposing the role of Cdc5 in coordinating the mitotic exit pathway and cytokinesis. At late anaphase/telophase, but before full spindle elongation and assembly of contractile ring, Cdc5 carries out two important functions. First, in a polo-box–independent manner, Cdc5 activates APC, which leads to inactivation of Cdc28/Clb2, thereby permitting mitotic exit. Second, in a polo-box–dependent manner, Cdc5 localizes at cytokinetic neck filaments and promotes the cytokinetic functions of septins.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195991&req=5

Figure 8: Model proposing the role of Cdc5 in coordinating the mitotic exit pathway and cytokinesis. At late anaphase/telophase, but before full spindle elongation and assembly of contractile ring, Cdc5 carries out two important functions. First, in a polo-box–independent manner, Cdc5 activates APC, which leads to inactivation of Cdc28/Clb2, thereby permitting mitotic exit. Second, in a polo-box–dependent manner, Cdc5 localizes at cytokinetic neck filaments and promotes the cytokinetic functions of septins.
Mentions: Our data suggest that Cdc5 plays dual roles in a late stage of M phase. We propose that, in addition to activation of APC, Cdc5 activity is required for proper function of septin ring structures during cytokinesis (Fig. 8). In this scenario, during or shortly after activation of APC, a fraction of Cdc5 relocalizes to bud-neck to carry out its cytokinetic function, an event that requires an intact polo-box. A dominant-negative cdc5ΔN, which localizes at the neck-filament, does not interfere with APC activation and mitotic exit pathway. However, it inhibits Cdc5 localization at the neck filaments, thereby impairing septin functions critical for cytokinesis. Our model also helps explain the phenotypes associated with overexpression of Cdc5 (Song et al. 2000) or an activated form of Plk (Lee et al. 1999). In both cases, unregulated Cdc5/Plk activity may have induced abnormally elongated buds by activation of APC, whereas ectopic septin rings may have arisen by reinforcing septin ring organization. Our data suggest that activation of the APC does not require a polo-box–dependent localization of Cdc5 at the septin rings, whereas overexpression of the polo-box domain is sufficient to inhibit cytokinesis. Thus, temporal and spatial regulation of Cdc5 may provide an important mechanism to coordinate mitotic exit pathway with initiation of cytokinesis.

Bottom Line: Overexpression of the COOH-terminal domain of Cdc5 (cdc5DeltaN), but not the corresponding polo-box mutant, resulted in connected cells.The polo-box-dependent interactions between Cdc5 and septins (Cdc11 and Cdc12) and genetic interactions between the dominant-negative cdc5DeltaN and Cyk2/Hof1 or Myo1 suggest that direct interactions between cdc5DeltaN and septins resulted in inhibition of Cyk2/Hof1- and Myo1-mediated cytokinetic pathways.Thus, we propose that Cdc5 may coordinate mitotic exit with cytokinesis by participating in both anaphase promoting complex activation and a polo-box-dependent cytokinetic pathway.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Metabolism, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

ABSTRACT
Coordination of mitotic exit with timely initiation of cytokinesis is critical to ensure completion of mitotic events before cell division. The Saccharomyces cerevisiae polo kinase Cdc5 functions in a pathway leading to the degradation of mitotic cyclin Clb2, thereby permitting mitotic exit. Here we provide evidence that Cdc5 also plays a role in regulating cytokinesis and that an intact polo-box, a conserved motif in the noncatalytic COOH-terminal domain of Cdc5, is required for this event. Depletion of Cdc5 function leads to an arrest in cytokinesis. Overexpression of the COOH-terminal domain of Cdc5 (cdc5DeltaN), but not the corresponding polo-box mutant, resulted in connected cells. These cells shared cytoplasms with incomplete septa, and possessed aberrant septin ring structures. Provision of additional copies of endogenous CDC5 remedied this phenotype, suggesting a dominant-negative inhibition of cytokinesis. The polo-box-dependent interactions between Cdc5 and septins (Cdc11 and Cdc12) and genetic interactions between the dominant-negative cdc5DeltaN and Cyk2/Hof1 or Myo1 suggest that direct interactions between cdc5DeltaN and septins resulted in inhibition of Cyk2/Hof1- and Myo1-mediated cytokinetic pathways. Thus, we propose that Cdc5 may coordinate mitotic exit with cytokinesis by participating in both anaphase promoting complex activation and a polo-box-dependent cytokinetic pathway.

Show MeSH
Related in: MedlinePlus