Cyclin-dependent kinase control of motile ciliogenesis
- University of Colorado School of Medicine, United States
- Stanford University, United States
- Columbia University Medical Center, United States
- Stanford University School of Medicine, United States
Abstract
Cycling cells maintain centriole number at precisely two per cell in part by limiting their duplication to S phase under the control of the cell cycle machinery. In contrast, postmitotic multiciliated cells (MCCs) uncouple centriole assembly from cell cycle progression and produce hundreds of centrioles in the absence of DNA replication to serve as basal bodies for motile cilia. Although some cell cycle regulators have previously been implicated in motile ciliogenesis, how the cell cycle machinery is employed to amplify centrioles is unclear. We use transgenic mice and primary airway epithelial cell culture to show that Cdk2, the kinase responsible for the G1 to S phase transition, is also required in MCCs to initiate motile ciliogenesis. While Cdk2 is coupled with Cyclins E and A2 during cell division, Cyclin A1 is required during ciliogenesis, contributing to an alternative regulatory landscape that facilitates centriole amplification without DNA replication.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Funding
National Institutes of Health (R01GM052022)
- Tim Stearns
National Institutes of Health (R01GM121424)
- Tim Stearns
National Institutes of Health (R01GM098582)
- Jeffrey D Axelrod
National Institutes of Health (1R01HD034915)
- Debra Wolgemuth
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures involving animals were approved by the Institutional Animal Care and Use Committee of Stanford University School of Medicine (#17926) in accordance with established guidelines for animal care.
Copyright
© 2018, Vladar 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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Cyclin-dependent kinase control of motile ciliogenesis
eLife 7:e36375.
https://doi.org/10.7554/eLife.36375
