Ubiquitin-proteasome system controls ciliogenesis at the initial step of axoneme extension

Kousuke Kasahara, Yoshitaka Kawakami, Tohru Kiyono, Shigenobu Yonemura, Yoshifumi Kawamura, Saho Era, Fumio Matsuzaki, Naoki Goshima and Masaki Inagaki ()
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Kousuke Kasahara: Aichi Cancer Center Research Institute
Yoshitaka Kawakami: Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology
Tohru Kiyono: National Cancer Center Research Institute
Shigenobu Yonemura: Electron Microscope Laboratory, RIKEN Center for Developmental Biology
Yoshifumi Kawamura: Japan Biological Informatics Consortium (JBiC)
Saho Era: Aichi Cancer Center Research Institute
Fumio Matsuzaki: Laboratory of Cell Asymmetry, RIKEN Center of Developmental Biology
Naoki Goshima: Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology
Masaki Inagaki: Aichi Cancer Center Research Institute

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: Abstract Primary cilia are microtubule-based sensory organelles that organize numerous key signals during developments and tissue homeostasis. Ciliary microtubule doublet, named axoneme, is grown directly from the distal end of mother centrioles through a multistep process upon cell cycle exit; however, the instructive signals that initiate these events are poorly understood. Here we show that ubiquitin-proteasome machinery removes trichoplein, a negative regulator of ciliogenesis, from mother centrioles and thereby causes Aurora-A inactivation, leading to ciliogenesis. Ciliogenesis is blocked if centriolar trichoplein is stabilized by treatment with proteasome inhibitors or by expression of non-ubiquitylatable trichoplein mutant (K50/57R). Started from two-stepped global E3 screening, we have identified KCTD17 as a substrate-adaptor for Cul3-RING E3 ligases (CRL3s) that polyubiquitylates trichoplein. Depletion of KCTD17 specifically arrests ciliogenesis at the initial step of axoneme extension through aberrant trichoplein-Aurora-A activity. Thus, CRL3-KCTD17 targets trichoplein to proteolysis to initiate the axoneme extension during ciliogenesis.

Date: 2014
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DOI: 10.1038/ncomms6081

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