title: Trichoplein and Aurora A block aberrant primary cilia assembly in proliferating cells.
abstract: The primary cilium is an antenna-like organelle that modulates differentiation, sensory functions, and signal transduction. After cilia are disassembled at the G0/G1 transition, formation of cilia is strictly inhibited in proliferating cells. However, the mechanisms of this inhibition are unknown. In this paper, we show that trichoplein disappeared from the basal body in quiescent cells, whereas it localized to mother and daughter centrioles in proliferating cells. Exogenous expression of trichoplein inhibited primary cilia assembly in serum-starved cells, whereas ribonucleic acid interference-mediated depletion induced primary cilia assembly upon cultivation with serum. Trichoplein controlled Aurora A (AurA) activation at the centrioles predominantly in G1 phase. In vitro analyses confirmed that trichoplein bound and activated AurA directly. Using trichoplein mutants, we demonstrate that the suppression of primary cilia assembly by trichoplein required its ability not only to localize to centrioles but also to bind and activate AurA. Trichoplein or AurA knockdown also induced G0/G1 arrest, but this phenotype was reversed when cilia formation was prevented by simultaneous knockdown of IFT-20. These data suggest that the trichoplein-AurA pathway is required for G1 progression through a key role in the continuous suppression of primary cilia assembly.
authors.affiliation: Division of Biochemistry, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Inoko
authors.forename: Makoto
authors.initials: M
authors.lastname: Matsuyama
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Goto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohmuro-Matsuyama
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Masato
authors.initials: M
authors.lastname: Enomoto
authors.forename: Miho
authors.initials: M
authors.lastname: Ibi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Urano
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yonemura
authors.forename: Tohru
authors.initials: T
authors.lastname: Kiyono
authors.forename: Ichiro
authors.initials: I
authors.lastname: Izawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Inagaki
mesh_terms: D064127:Aurora Kinases; D015153:Blotting, Western; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002502:Centrioles / Q000378:metabolism*; D002923:Cilia / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D008870:Microtubules / Q000378:metabolism; D009024:Morphogenesis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C502303:TCHP protein, human; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases