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Elife. 2018 Aug 28;7. pii: e36375. doi: 10.7554/eLife.36375.

Cyclin-dependent kinase control of motile ciliogenesis.

Author information

1
Department of Pathology, Stanford University School of Medicine, Stanford, United States.
2
Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, United States.
3
Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, United States.
4
Department of Biology, Stanford University, Stanford, United States.
5
Center for Radiological Research, Columbia University Medical Center, New York, United States.
6
Department of Genetics & Development, Columbia University Medical Center, New York, United States.
7
Department of Genetics, Stanford University School of Medicine, Stanford, 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.

KEYWORDS:

Cdk2; Cyclin A1; cell biology; cell cycle; centriole; cilia; ciliogenesis; mouse

PMID:
30152757
PMCID:
PMC6145839
DOI:
10.7554/eLife.36375
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

EV, MS, MS, GS, XW, DW, TS, JA No competing interests declared

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