Centrosome/Cell Cycle Uncoupling and Elimination in the Endoreduplicating Intestinal Cells of C. elegans

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.

SPD-2/CEP192 and CDK Are Limiting for Microtubule-Organizing Center Function at the Centrosome

“…Together, these data indicate that the apical surface of intestinal cells becomes an MTOC during polarization and that the centrosome is inactivated as an MTOC. Intriguingly, a recent report found that intestinal centrosomes are eliminated during larval stages, suggesting that centrosomes are dispensable once they are no longer needed for mitosis [14].…”

Cyclin-dependent kinase control of motile ciliogenesis

“…It will be interesting to compare MCC mechanisms to those operating in other cells with alternative cell cycles or where DNA and centriole duplication are uncoupled. These include male germ cells in which meiosis is regulated by Cdk2-Ccna1 ( Liu et al, 1998 ) and endocycling cells that undergo many rounds of DNA replication without mitosis ( Lu and Roy, 2014 ). With growing attention to MCCs in various tissues, improved understanding of the motile ciliogenesis pathway is an important goal.…”

Microtubule-organizing centers: from the centrosome to non-centrosomal sites

“…For example, cells exclusively containing ncMTOCs completely inactivate microtubule nucleation and anchoring at the centrosome as is seen in myotubes, rat and Drosophila neurons, and in some C. elegans and Drosophila epithelial cells [27,66,67]. Centrosomes in C. elegans embryonic intestinal cells or Drosophila tracheal cells lose PCM association and the ability to nucleate microtubules [13,14,54,68]. In both cell types, γ–TuRCs move away from the centrosome, and in Drosophila tracheal cells, this release requires the microtubule severing protein spastin.…”