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Centrosome/Cell cycle uncoupling and elimination in the endoreduplicating intestinal cells of C. elegans.

Lu Y, Roy R - PLoS ONE (2014)

Bottom Line: The centrioles then become refractory to S phase regulators that would normally promote duplication during the first endocycle, after which they are eliminated during the L2 stage.Furthermore, we show that SPD-2 plays a central role in the numeral regulation of centrioles as a potential target of CDK activity.On the other hand, the phosphorylation on SPD-2 by Polo-like kinase, the transcriptional regulation of genes that affect centriole biogenesis, and the ubiquitin/proteasome degradation pathway, contribute collectively to the final elimination of the centrioles during the L2 stage.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, The Developmental Biology Research Initiative, McGill University, Montreal, Quebec, Canada.

ABSTRACT
The centrosome cycle is most often coordinated with mitotic cell division through the activity of various essential cell cycle regulators, consequently ensuring that the centriole is duplicated once, and only once, per cell cycle. However, this coupling can be altered in specific developmental contexts; for example, multi-ciliated cells generate hundreds of centrioles without any S-phase requirement for their biogenesis, while Drosophila follicle cells eliminate their centrosomes as they begin to endoreduplicate. In order to better understand how the centrosome cycle and the cell cycle are coordinated in a developmental context we use the endoreduplicating intestinal cell lineage of C. elegans to address how novel variations of the cell cycle impact this important process. In C. elegans, the larval intestinal cells undergo one nuclear division without subsequent cytokinesis, followed by four endocycles that are characterized by successive rounds of S-phase. We monitored the levels of centriolar/centrosomal markers and found that centrosomes lose their pericentriolar material following the nuclear division that occurs during the L1 stage and is thereafter never re-gained. The centrioles then become refractory to S phase regulators that would normally promote duplication during the first endocycle, after which they are eliminated during the L2 stage. Furthermore, we show that SPD-2 plays a central role in the numeral regulation of centrioles as a potential target of CDK activity. On the other hand, the phosphorylation on SPD-2 by Polo-like kinase, the transcriptional regulation of genes that affect centriole biogenesis, and the ubiquitin/proteasome degradation pathway, contribute collectively to the final elimination of the centrioles during the L2 stage.

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A model to depict centriole uncoupling and elimination in the postembryonic C. elegans intestine.The complete postembryonic lineage of single intestinal cell in the wide type animals is shown. Each SPD-2 focus (green) represents a centriole pair. Centrioles undergo duplication and separation during the L1 nuclear division. The centrioles then lose their PCM during anaphase and undergo cell cycle “uncoupling” whereby centrioles are unaffected by the oscillations of successive endocycle S-phases. These events precede the diffusion of SPD-2 into the intestinal nuclei followed by its eventual elimination. The effects of SPD-2 variants or genetic backgrounds on centriole duplication/stability are highlighted at the relevant developmental stages. Substituting Serine 545 with Alanine on SPD-2 results in centriole duplication failure, whereas replacing Serine 545 with Glutamic Acid or, alternatively in lin-35 mutants, centrioles overduplicate. SPD-2 becomes stabilized when pbs-3 is abrogated or if SPD-2 S357 is converted to a phosphomimetic residue.
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pone-0110958-g008: A model to depict centriole uncoupling and elimination in the postembryonic C. elegans intestine.The complete postembryonic lineage of single intestinal cell in the wide type animals is shown. Each SPD-2 focus (green) represents a centriole pair. Centrioles undergo duplication and separation during the L1 nuclear division. The centrioles then lose their PCM during anaphase and undergo cell cycle “uncoupling” whereby centrioles are unaffected by the oscillations of successive endocycle S-phases. These events precede the diffusion of SPD-2 into the intestinal nuclei followed by its eventual elimination. The effects of SPD-2 variants or genetic backgrounds on centriole duplication/stability are highlighted at the relevant developmental stages. Substituting Serine 545 with Alanine on SPD-2 results in centriole duplication failure, whereas replacing Serine 545 with Glutamic Acid or, alternatively in lin-35 mutants, centrioles overduplicate. SPD-2 becomes stabilized when pbs-3 is abrogated or if SPD-2 S357 is converted to a phosphomimetic residue.

Mentions: During the development of many organisms however, the mitotic cell cycle is replaced by the endocycle: an alternative means to provide tissue mass or to increase nuclear output/volume [32]. We were interested in how centrioles would respond to this modified cell cycle. We found that the centrioles appear to undergo a cell cycle uncoupling event shortly after the intestinal nuclear division. This uncoupling is contingent on the transition from mitotic cell division to an endocycle program at the end of the L1 stage. Following this division the centrioles are no longer duplicated and are eliminated during the L2 stage; an event that is an intrinsic developmental fate in these endocycling cells (Figure 8).


Centrosome/Cell cycle uncoupling and elimination in the endoreduplicating intestinal cells of C. elegans.

Lu Y, Roy R - PLoS ONE (2014)

A model to depict centriole uncoupling and elimination in the postembryonic C. elegans intestine.The complete postembryonic lineage of single intestinal cell in the wide type animals is shown. Each SPD-2 focus (green) represents a centriole pair. Centrioles undergo duplication and separation during the L1 nuclear division. The centrioles then lose their PCM during anaphase and undergo cell cycle “uncoupling” whereby centrioles are unaffected by the oscillations of successive endocycle S-phases. These events precede the diffusion of SPD-2 into the intestinal nuclei followed by its eventual elimination. The effects of SPD-2 variants or genetic backgrounds on centriole duplication/stability are highlighted at the relevant developmental stages. Substituting Serine 545 with Alanine on SPD-2 results in centriole duplication failure, whereas replacing Serine 545 with Glutamic Acid or, alternatively in lin-35 mutants, centrioles overduplicate. SPD-2 becomes stabilized when pbs-3 is abrogated or if SPD-2 S357 is converted to a phosphomimetic residue.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215990&req=5

pone-0110958-g008: A model to depict centriole uncoupling and elimination in the postembryonic C. elegans intestine.The complete postembryonic lineage of single intestinal cell in the wide type animals is shown. Each SPD-2 focus (green) represents a centriole pair. Centrioles undergo duplication and separation during the L1 nuclear division. The centrioles then lose their PCM during anaphase and undergo cell cycle “uncoupling” whereby centrioles are unaffected by the oscillations of successive endocycle S-phases. These events precede the diffusion of SPD-2 into the intestinal nuclei followed by its eventual elimination. The effects of SPD-2 variants or genetic backgrounds on centriole duplication/stability are highlighted at the relevant developmental stages. Substituting Serine 545 with Alanine on SPD-2 results in centriole duplication failure, whereas replacing Serine 545 with Glutamic Acid or, alternatively in lin-35 mutants, centrioles overduplicate. SPD-2 becomes stabilized when pbs-3 is abrogated or if SPD-2 S357 is converted to a phosphomimetic residue.
Mentions: During the development of many organisms however, the mitotic cell cycle is replaced by the endocycle: an alternative means to provide tissue mass or to increase nuclear output/volume [32]. We were interested in how centrioles would respond to this modified cell cycle. We found that the centrioles appear to undergo a cell cycle uncoupling event shortly after the intestinal nuclear division. This uncoupling is contingent on the transition from mitotic cell division to an endocycle program at the end of the L1 stage. Following this division the centrioles are no longer duplicated and are eliminated during the L2 stage; an event that is an intrinsic developmental fate in these endocycling cells (Figure 8).

Bottom Line: The centrioles then become refractory to S phase regulators that would normally promote duplication during the first endocycle, after which they are eliminated during the L2 stage.Furthermore, we show that SPD-2 plays a central role in the numeral regulation of centrioles as a potential target of CDK activity.On the other hand, the phosphorylation on SPD-2 by Polo-like kinase, the transcriptional regulation of genes that affect centriole biogenesis, and the ubiquitin/proteasome degradation pathway, contribute collectively to the final elimination of the centrioles during the L2 stage.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, The Developmental Biology Research Initiative, McGill University, Montreal, Quebec, Canada.

ABSTRACT
The centrosome cycle is most often coordinated with mitotic cell division through the activity of various essential cell cycle regulators, consequently ensuring that the centriole is duplicated once, and only once, per cell cycle. However, this coupling can be altered in specific developmental contexts; for example, multi-ciliated cells generate hundreds of centrioles without any S-phase requirement for their biogenesis, while Drosophila follicle cells eliminate their centrosomes as they begin to endoreduplicate. In order to better understand how the centrosome cycle and the cell cycle are coordinated in a developmental context we use the endoreduplicating intestinal cell lineage of C. elegans to address how novel variations of the cell cycle impact this important process. In C. elegans, the larval intestinal cells undergo one nuclear division without subsequent cytokinesis, followed by four endocycles that are characterized by successive rounds of S-phase. We monitored the levels of centriolar/centrosomal markers and found that centrosomes lose their pericentriolar material following the nuclear division that occurs during the L1 stage and is thereafter never re-gained. The centrioles then become refractory to S phase regulators that would normally promote duplication during the first endocycle, after which they are eliminated during the L2 stage. Furthermore, we show that SPD-2 plays a central role in the numeral regulation of centrioles as a potential target of CDK activity. On the other hand, the phosphorylation on SPD-2 by Polo-like kinase, the transcriptional regulation of genes that affect centriole biogenesis, and the ubiquitin/proteasome degradation pathway, contribute collectively to the final elimination of the centrioles during the L2 stage.

Show MeSH
Related in: MedlinePlus