Cyclin-dependent kinase control of motile ciliogenesis

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Centrioles / drug effects
  • Centrioles / metabolism
  • Cilia / drug effects
  • Cilia / metabolism*
  • Cyclin A1 / metabolism
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 2 / metabolism*
  • Epithelial Cells / metabolism
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitosis / drug effects
  • Movement*
  • Mutation / genetics
  • Organogenesis* / drug effects
  • Protein Transport / drug effects
  • Purines / pharmacology
  • Receptors, Notch / metabolism
  • Signal Transduction / drug effects
  • Trachea / metabolism
  • Trachea / ultrastructure
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • 4-(6-cyclohexylmethoxy-9H-purin-2-ylamino)-N,N-diethylbenzamide
  • Cyclin A1
  • Cyclin E
  • Purines
  • Receptors, Notch
  • Cyclin-Dependent Kinase 2