A novel Cep120-dependent mechanism inhibits centriole maturation in quiescent cells
- Washington University in St Louis, United States
Abstract
The two centrioles of the centrosome in quiescent cells are inherently asymmetric structures that differ in age, morphology and function. How these asymmetric properties are established and maintained during quiescence remains unknown. Here we show that a daughter centriole-associated ciliopathy protein, Cep120, plays a critical inhibitory role at daughter centrioles. Depletion of Cep120 in quiescent mouse and human cells causes accumulation of pericentriolar material (PCM) components including Pericentrin, Cdk5Rap2, Ninein and Cep170. The elevated PCM levels result in increased microtubule-nucleation activity at the centrosome. Consequently, loss of Cep120 leads to aberrant dynein-dependent trafficking of centrosomal proteins, dispersal of centriolar satellites, and defective ciliary assembly and signaling. Our results indicate that Cep120 helps to maintain centrosome homeostasis by inhibiting untimely maturation of the daughter centriole, and defines a potentially new molecular defect underlying the pathogenesis of ciliopathies such as Jeune asphyxiating thoracic dystrophy and Joubert syndrome.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Rashmi Nanjundappa
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK108005)
- Moe R Mahjoub
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Betleja et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A novel Cep120-dependent mechanism inhibits centriole maturation in quiescent cells
eLife 7:e35439.
https://doi.org/10.7554/eLife.35439
