title: The Ciliopathy-Associated Cep104 Protein Interacts with Tubulin and Nek1 Kinase.
abstract: 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.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Caezar
authors.initials: C
authors.lastname: Al-Jassar
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Antonina
authors.initials: A
authors.lastname: Andreeva
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Deepak D
authors.initials: DD
authors.lastname: Barnabas
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: McLaughlin
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Johnson
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Minmin
authors.initials: M
authors.lastname: Yu
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: vanbreug@mrc-lmb.cam.ac.uk.
authors.forename: Mark
authors.initials: M
authors.lastname: van Breugel
mesh_terms: D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008958:Models, Molecular; D000072380:NIMA-Related Kinase 1 / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D014404:Tubulin / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: C467559:CCP110 protein, human; D018797:Cell Cycle Proteins; C000624120:Cep104 protein, human; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D014404:Tubulin; C000606914:NEK1 protein, human; D000072380:NIMA-Related Kinase 1
keywords: CP110; Cep104; Nek1; TOG; basal body; centriole; cilia; tubulin; zinc finger