The Ciliopathy-Associated Cep104 Protein Interacts with Tubulin and Nek1 Kinase

• Published in: Structure (London) 2017-01, Vol.25 (1), p.146-156
• Main Authors: Al-Jassar, Caezar, Andreeva, Antonina, Barnabas, Deepak D., McLaughlin, Stephen H., Johnson, Christopher M., Yu, Minmin, van Breugel, Mark
• Format: Article
• Language: English
• Subjects: basal body; Binding Sites; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - metabolism; centriole; Cep104; cilia; Cilia - metabolism; CP110; Crystallography, X-Ray; Humans; Microtubule-Associated Proteins - metabolism; Models, Molecular; Nek1; NIMA-Related Kinase 1 - metabolism; Phosphoproteins - metabolism; Protein Binding; Protein Structure, Secondary; TOG; tubulin; Tubulin - metabolism; zinc finger; Zinc Fingers
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2016.11.014

Cilia are thin cell projections with essential roles in cell motility, fluid movement, sensing, and signaling. They are templated from centrioles that dock against the plasma membrane and subsequently extend their peripheral microtubule array. The molecular mechanisms underpinning cilia assembly are incompletely understood. Cep104 is a key factor involved in cilia formation and length regulation that rides on the ends of elongating and shrinking cilia. It is mutated in Joubert syndrome, a genetically heterogeneous ciliopathy. Here we provide structural and biochemical data that Cep104 contains a tubulin-binding TOG (tumor overexpressed gene) domain and a novel C2HC zinc finger array. Furthermore, we identify the kinase Nek1, another ciliopathy-associated protein, as a potential binding partner of this array. Finally, we show that Nek1 competes for binding to Cep104 with the distal centriole-capping protein CP110. Our data suggest a model for Cep104 activity during ciliogenesis and provide a novel link between Cep104 and Nek1. [Display omitted] •The centriolar protein Cep104 contains a tubulin-binding TOG domain•Nek1 kinase binds to a zinc finger array in Cep104•Nek1 and the centriole-capping protein CP110 compete for binding to Cep104•The Cep104's zinc finger array represents a novel arrangement of C2HC zinc fingers Cep104 is essential for cilia formation. Al-Jassar et al. provide insights into Cep104's function by showing that it contains a tubulin-binding TOG domain. The authors also found that the ciliopathy-associated Nek1 kinase binds to Cep104 and that the centriole-capping protein CP110 competes for this binding.