Cyclin-dependent kinase control of motile ciliogenesis

ELife
Eszter K VladarJeffrey D Axelrod

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.

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Citations

Mar 25, 2019·Biology of the Cell·Adel Al JordAlice Meunier
Apr 27, 2019·ELife·Rashmi NanjundappaMoe R Mahjoub
Aug 20, 2019·Cellular and Molecular Life Sciences : CMLS·Eva QuandtJosep Clotet
Sep 12, 2019·Scientific Reports·Olivier MerceyAlice Meunier
Dec 4, 2019·Nature Cell Biology·Olivier MerceyAndrew J Holland
Sep 12, 2020·Cellular and Molecular Life Sciences : CMLS·Lance Lee, Lawrence E Ostrowski
Jan 3, 2019·Annual Review of Biochemistry·David K Breslow, Andrew J Holland
May 6, 2020·Scientific Reports·Lenka RadonovaMartin Anger
Dec 5, 2020·Current Opinion in Neurobiology·Gonzalo Ortiz-Álvarez, Nathalie Spassky

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Methods Mentioned

BETA
PCR
FACS
transfection
scanning electron microscopy
scraping
Assay

Software Mentioned

GraphPad
Prism7
ImageJ
Leica LAS X

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