Centrioles: some self-assembly required

Abstract

Centrioles play an important role in organizing microtubules and are precisely duplicated once per cell cycle. New (daughter) centrioles typically arise in association with existing (mother) centrioles (canonical assembly), suggesting that mother centrioles direct the formation of daughter centrioles. However, under certain circumstances, centrioles can also selfassemble free of an existing centriole (de novo assembly). Recent work indicates that the canonical and de novo pathways utilize a common mechanism and that a mother centriole spatially constrains the self-assembly process to occur within its immediate vicinity. Other recently identified mechanisms further regulate canonical assembly so that during each cell cycle, one and only one daughter centriole is assembled per mother centriole.

Figure 1

The molecular pathway of centriole assembly is conserved between C. elegans and humans. (A) The ultrastructurally-defined steps of the centriole assembly pathway in C. elegans embryos are shown at the top, and the centriole assembly factors required at various steps of this process are shown below. Initially, SAS-4 (blue) is not stably associated with the forming centriole but the addition of centriole microtubules by γ-tubulin, and possibly other PCM components, stabilizes SAS-4 (black). A similar mechanism appear to operate in human cells where the ZYG-1-related kinase Plk4 acts upstream of SAS-4 (CPAP) and SAS-6 orthologs. Cross-sectional views of centrioles in C. elegans (B) and vertebrates (C) are shown. The C. elegans centriole contains a central tube surrounded by singlet microtubules (green) while human cells possess microtubule triplets but lack a central tube.

Figure 2

Canonical and de novo centriole assembly. In the canonical pathway, (1) separase is activated at the metaphase-to-anaphase transition and drives the disengagement of mother and daughter centrioles thereby licensing them for replication (green shading). (2) During S phase, centriole precursors (grey disks) form in the PCM (purple). The extent of the PCM is reduced during interphase, which might serve to limit the number of precursors that form. (3) This initial phase of centriole assembly ends when a single precursor engages each of the mother centrioles. Upon engagement, each mother centriole loses its license (red shading) and engagement with additional precursors is blocked. (4) Engagement stabilizes the precursor and allows the assembly process to complete. (5) Segregation of centriole pairs to the spindle poles re-establishes the original number of centrioles per cell. In cases where centriole are lost or damaged, centrioles may be regenerated via the de novo pathway. (6) Loss of centrioles results in dispersion of the PCM. (7) The PCM randomly aggregates in the cytoplasm whereupon precursors can form. (8) Some of these precursors complete assembly leading to a random number of centrioles. Formation of just a single centriole can aggregate the PCM shutting off further de novo assembly. These centrioles then re-enter the canonical pathway.