Abstract
Centrosomes consist of two centrioles embedded in pericentriolar material and function as the main microtubule organising centres in dividing animal cells. They ensure proper formation and orientation of the mitotic spindle and are therefore essential for the maintenance of genome stability. Centrosome function is crucial during embryonic development, highlighted by the discovery of mutations in genes encoding centrosome or spindle pole proteins that cause autosomal recessive primary microcephaly, including Cep63 and Cep152. In this study we show that Cep63 functions to ensure that centriole duplication occurs reliably in dividing mammalian cells. We show that the interaction between Cep63 and Cep152 can occur independently of centrosome localisation and that the two proteins are dependent on one another for centrosomal localisation. Further, both mouse and human Cep63 and Cep152 cooperate to ensure efficient centriole duplication by promoting the accumulation of essential centriole duplication factors upstream of SAS-6 recruitment and procentriole formation. These observations describe the requirement for Cep63 in maintaining centriole number in dividing mammalian cells and further establish the order of events in centriole formation.
Highlights
The centrosome is the primary microtubule organising centre in dividing cells and is composed of 2 centrioles that are embedded in pericentriolar material (PCM)
Using recombinant proteins incubated in egg extracts, we found that the Xenopus laevis Cep63 and Cep152 orthologues interact, indicating that the Cep63-Cep152 interaction can occur independently of centrosome localisation (XCep63 and XCep152, Figure S1C)
These data indicate that the interaction between Cep63 and Cep152 is required for the localisation of Cep152 to the centrosome, consistent with previous data showing that Cep63 recruits Cep152 to the centrosome [24,30]
Summary
The centrosome is the primary microtubule organising centre in dividing cells and is composed of 2 centrioles that are embedded in pericentriolar material (PCM). Centrioles are cylindrical structures composed of triplet and doublet microtubules, arranged with a 9fold radial symmetry [1]. In addition to their essential role in the formation of the centrosome, centrioles are required for the assembly of cilia and flagella [1,2]. Centriole number is under tight regulation in dividing cells. A newly born cell in the G1 phase of the cell cycle contains two disengaged centrioles, both competent to organise PCM and form a new procentriole at, and perpendicular to, the proximal end [3]. The strict regulation of centriole number is crucial for the accurate and symmetrical formation of the mitotic spindle and precise, reproducible segregation of the genome during mitosis
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