Abstract
SummaryCentrioles form centrosomes and cilia, and defects in any of these three organelles are associated with human disease [1]. Centrioles duplicate once per cell cycle, when a mother centriole assembles an adjacent daughter during S phase. Daughter centrioles cannot support the assembly of another daughter until they mature into mothers during the next cell cycle [2–5]. The molecular nature of this daughter-to-mother transition remains mysterious. Pioneering studies in C. elegans identified a set of core proteins essential for centriole duplication [6–12], and a similar set have now been identified in other species [10, 13–18]. The protein kinase ZYG-1/Sak/Plk4 recruits the inner centriole cartwheel components SAS-6 and SAS-5/Ana2/STIL, which then recruit SAS-4/CPAP, which in turn helps assemble the outer centriole microtubules [19, 20]. In flies and humans, the Asterless/Cep152 protein interacts with Sak/Plk4 and Sas-4/CPAP and is required for centriole duplication, although its precise role in the assembly pathway is unclear [21–24]. Here, we show that Asl is not incorporated into daughter centrioles as they assemble during S phase but is only incorporated once mother and daughter separate at the end of mitosis. The initial incorporation of Asterless (Asl) is irreversible, requires DSas-4, and, crucially, is essential for daughter centrioles to mature into mothers that can support centriole duplication. We therefore propose a “dual-licensing” model of centriole duplication, in which Asl incorporation provides a permanent primary license to allow new centrioles to duplicate for the first time, while centriole disengagement provides a reduplication license to allow mother centrioles to duplicate again.
Highlights
Daughter Centrioles Incorporate DSas-4, but Not Asl, during Their Assembly To better understand how Asl and DSas-4 might function together in fly centriole duplication, we followed the behavior of GFP-fusions of these proteins in centrosomes during the rapid, early, mitotic cycles in living syncytial blastoderm Drosophila embryos
In early S phase, just after the centrosomes have separated (Figure 1A, t = 0 s), the level of DSas-4-GFP fluorescence was similar at the two centrosomes and gradually increased during S phase, as new daughter centrioles assembled (Figures 1A and 1B)
This behavior suggests that a pool of DSas-4 is stably incorporated into daughter centrioles as they form but that some ‘‘excess’’ DSas-4 is recruited during S phase and lost during mitosis (Figure 1E)
Summary
We conclude that Asl is essential for centriole duplication [21], Asl-GFP is surprisingly not incorporated into daughter centrioles as they assemble during S phase but only starts to be incorporated at about the time they separate from their mothers at the end of mitosis.
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