Ubiquitin-proteasome system controls ciliogenesis at the initial step of axoneme extension.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Axoneme, Centrioles, Cilia, Cullin Proteins, Humans, Proteasome Endopeptidase Complex, Ubiquitin
Adaptor Proteins, Signal Transducing, Axoneme, Centrioles, Cilia, Cullin Proteins, Humans, Proteasome Endopeptidase Complex, Ubiquitin
Nat Commun
Date: Oct. 02, 2014
PubMed ID: 25270598
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