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

    Research output: Contribution to journalArticlepeer-review

    27 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)927-940
    Number of pages14
    JournalGenes to Cells
    Volume19
    Issue number12
    DOIs
    Publication statusPublished - 2014 Dec 1

    ASJC Scopus subject areas

    • Genetics
    • Cell Biology

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