Control of mitotic and meiotic centriole duplication by the Plk4-related kinase ZYG-1

Abstract

SummaryCentriole duplication is of crucial importance during both mitotic and male meiotic divisions, but it is currently not known whether this process is regulated differently during the two modes of division. In Caenorhabditis elegans, the kinase ZYG-1 plays an essential role in both mitotic and meiotic centriole duplication. We have found that the C-terminus of ZYG-1 is necessary and sufficient for targeting to centrosomes and is important for differentiating mitotic and meiotic centriole duplication. Small truncations of the Cterminus dramatically lower the level of ZYG-1 at mitotic centrosomes but have little effect on the level of ZYG-1 at meiotic centrosomes. Interestingly, truncation of ZYG-1 blocks centrosome duplication in the mitotic cycle but leads to centrosome amplification in the meiotic cycle. Meiotic centriole amplification appears to result from the overduplication of centrioles during meiosis I and leads to the formation of multipolar meiosis II spindles. The extra centrioles also disrupt spermatogenesis by inducing the formation of supernumerary fertilization-competent spermatids that contain abnormal numbers of chromosomes and centrioles. Our data reveal differences in the regulation of mitotic and meiotic centrosome duplication, particularly with regard to ZYG-1 activity, and reveal an important role for centrosomes in spermatid formation.

The C. elegans F-box proteins LIN-23 and SEL-10 antagonize centrosome duplication by regulating ZYG-1 levels

“…It is therefore possible that the differences we have observed reflect a differential regulation of centrosome duplication in the embryo compared with the soma. In fact, tissue-specific adaptations of the regulation of centrosome duplication have been observed previously in Drosophila and in C. elegans (Peel et al, 2007;Peters et al, 2010).…”

“…This allowed us to confirm that loss of SEL-10 during spermatogenesis was responsible for the relatively high levels of centrosome duplication failure in the embryos of self-fertilizing zyg-1(it25); sel-10(ok1632) hermaphrodites. This situation is reminiscent of class II mutations in zyg-1 which show differential effects in spermatogenesis and the embryo (Peters, 2010). After restoring paternal SEL-10 activity, the sel-10(ok1632) allele robustly rescues centrosome duplication failure (60% duplication, n535; Fig.…”

“…To analyze the dynamic changes in ZYG-1 levels we used a GFP reporter in which GFP was fused to the C-terminal (non-kinase) portion of ZYG-1 (hereafter GFP::cZYG-1) (supplementary material Fig. S2) (Peters et al, 2010). The localization and cell cycledependent levels of GFP::cZYG-1 correlated with endogenous ZYG-1 (Fig.…”

“…The ZYG-1 protein contains a consensus sequence for Slimbbinding (Peters et al, 2010). However, when we compared ZYG-1 sequences among various nematode species we noticed that the Slimb-binding motif is not conserved in other Caenorhabditis LIN-23 and SEL-10 regulate ZYG-1 levels 3537 species including the nearest relative C. briggsae (supplementary material Fig.…”

Manipulation of Karyotype inCaenorhabditis elegansReveals Multiple Inputs Driving Pairwise Chromosome Synapsis During Meiosis

“…In contrast, spermatocytes undergo symmetric meiotic divisions using spindles with centrosomes at their poles ( Figure 2A). Moreover, both products of spermatocyte meiosis I undergo meiosis II in parallel, and following anaphase II, a specialized budding division process, directed by the centrioles (Peters et al 2010), packages each of the four meiotic haploid products into individual spermatids, leaving behind microtubules and other cellular components in a structure known as the residual body (Shakes et al 2009). …”