Binding to Cep164, but not EB1, is essential for centriolar localization of TTBK2 and its function in ciliogenesis

Toshiaki Oda, Shuhei Chiba, Tomoaki Nagai, Kensaku Mizuno

研究成果: Article査読

33 被引用数 (Scopus)

抄録

Primary cilia are formed by extending the microtubule-based axoneme from the mother centriole-derived basal body. Recruitment of Tau tubulin kinase-2 (TTBK2) to the mother centriole and subsequent removal of CP110 and its interactor Cep97 are crucial for the initiation of ciliogenesis. We analyzed the roles of two TTBK2-binding proteins, EB1 and Cep164, in centriolar localization of TTBK2. TTBK2 bound EB1 and Cep164 through its SxIP motifs and a proline-rich motif, respectively. Using TTBK2 variants that contained mutations in the SxIP or proline-rich motifs, we obtained evidence that Cep164, but not EB1, is essential for centriolar localization of TTBK2. Depletion of TTBK2 inhibited CP110 removal and ciliogenesis, whereas expression of wild-type TTBK2, but not non-Cep164-binding mutants, rescued CP110 removal and ciliogenesis in TTBK2-depleted cells. Therefore, Cep164 binding is essential for the function of TTBK2 in promoting CP110 removal and ciliogenesis. We also provide evidence that TTBK2 has the potential to effectively phosphorylate Cep164 and Cep97 and inhibits the interaction between Cep164 and its binding partner Dishevelled-3 (an important regulator of ciliogenesis) in a kinase activity-dependent manner.

本文言語English
ページ(範囲)927-940
ページ数14
ジャーナルGenes to Cells
19
12
DOI
出版ステータスPublished - 2014 12月 1

ASJC Scopus subject areas

  • 遺伝学
  • 細胞生物学

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