No abstract

The number of centrioles is tightly controlled to ensure bipolar spindle assembly, which is a prerequisite to maintain genome integrity. However, our understanding of the fundamental principle that governs the formation of a single procentriole per parental centriole is incomplete. Here, we show that the local restriction of Plk4, a master regulator of the procentriole formation, is achieved by a bimodal interaction of STIL with Plk4. We demonstrate that the conserved short coiled-coil region of STIL binds to and protects Plk4 from protein degradation at the site of procentriole formation. On the other hand, the conserved C-terminal region of STIL named truncated in microcephaly (TIM) domain promotes autophosphorylation and degradation of adjacent Plk4 by the direct interaction. Thus, we propose that positive and negative regulation based on the bimodal binding of Plk4 and STIL ensures the formation of a single procentriole per parental centriole.

Centrioles surrounded by pericentriolar material (PCM) serve as the core structure of the centrosome. A newly formed daughter centriole grows into a functional mother centriole. However, the underlying mechanisms remain poorly understood. Here we show that Cep295, an evolutionarily conserved protein, is required for generation of a bona fide mother centriole organizing a functional centrosome. We find that Cep295 is recruited to the proximal centriole wall in the early stages of procentriole assembly. Cep295 then acts as a scaffold for the proper assembly of the daughter centriole. We also find that Cep295 binds directly to and recruits Cep192 onto the daughter centriole wall, which presumably endows the function of the new mother centriole for PCM assembly, microtubule-organizing centre activity and the ability for centriole formation. These findings led us to propose that Cep295 acts upstream of the conserved pathway for centriole formation and promotes the daughter-to-mother centriole conversion.