Bimodal Binding of STIL to Plk4 Controls Proper Centriole Copy Number

• Published in: Cell reports (Cambridge) 2018-06, Vol.23 (11), p.3160-3169.e4
• Main Authors: Ohta, Midori, Watanabe, Koki, Ashikawa, Tomoko, Nozaki, Yuka, Yoshiba, Satoko, Kimura, Akatsuki, Kitagawa, Daiju
• Format: Article
• Language: English
• Subjects: cell division; centriole duplication; centrosome; Plk4; STIL
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.05.030

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. [Display omitted] •Plk4 asymmetry is achieved prior to procentriole formation•Autophosphorylation of Plk4 is critical for the restriction of Plk4 at a single site•Bimodal binding of STIL to Plk4 regulates the activation and degradation of Plk4•The TIM domain of STIL limits Plk4 at centrioles and the number of procentrioles Ohta et al. show that Plk4 asymmetrically localizes around mother centrioles before the onset of procentriole formation. Furthermore, they reveal that bimodal binding of STIL to Plk4 restricts Plk4 localization at a single site and thus ensures formation of a single procentriole per mother centriole.