Cyclin-dependent kinase control of motile ciliogenesis
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 centri...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/36375 |
| _version_ | 1811202629503549440 |
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| author | Eszter K Vladar Miranda B Stratton Maxwell L Saal Glicella Salazar-De Simone Xiangyuan Wang Debra Wolgemuth Tim Stearns Jeffrey D Axelrod |
| author_facet | Eszter K Vladar Miranda B Stratton Maxwell L Saal Glicella Salazar-De Simone Xiangyuan Wang Debra Wolgemuth Tim Stearns Jeffrey D Axelrod |
| author_sort | Eszter K Vladar |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:42:07Z |
| format | Article |
| id | doaj.art-6ea2e27ed75e4c31bc660ad9a6e8aae3 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:42:07Z |
| publishDate | 2018-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6ea2e27ed75e4c31bc660ad9a6e8aae32022-12-22T03:51:17ZengeLife Sciences Publications LtdeLife2050-084X2018-08-01710.7554/eLife.36375Cyclin-dependent kinase control of motile ciliogenesisEszter K Vladar0https://orcid.org/0000-0002-4160-8894Miranda B Stratton1Maxwell L Saal2Glicella Salazar-De Simone3Xiangyuan Wang4Debra Wolgemuth5Tim Stearns6https://orcid.org/0000-0002-0671-6582Jeffrey D Axelrod7Department of Pathology, Stanford University School of Medicine, Stanford, United States; Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, United States; Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, United StatesDepartment of Biology, Stanford University, Stanford, United StatesDivision of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, United States; Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, United StatesCenter for Radiological Research, Columbia University Medical Center, New York, United StatesDepartment of Genetics & Development, Columbia University Medical Center, New York, United StatesDepartment of Genetics & Development, Columbia University Medical Center, New York, United StatesDepartment of Biology, Stanford University, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United StatesDepartment of Pathology, Stanford University School of Medicine, Stanford, United StatesCycling 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.https://elifesciences.org/articles/36375ciliaciliogenesiscentriolecell cycleCdk2Cyclin A1 |
| spellingShingle | Eszter K Vladar Miranda B Stratton Maxwell L Saal Glicella Salazar-De Simone Xiangyuan Wang Debra Wolgemuth Tim Stearns Jeffrey D Axelrod Cyclin-dependent kinase control of motile ciliogenesis eLife cilia ciliogenesis centriole cell cycle Cdk2 Cyclin A1 |
| title | Cyclin-dependent kinase control of motile ciliogenesis |
| title_full | Cyclin-dependent kinase control of motile ciliogenesis |
| title_fullStr | Cyclin-dependent kinase control of motile ciliogenesis |
| title_full_unstemmed | Cyclin-dependent kinase control of motile ciliogenesis |
| title_short | Cyclin-dependent kinase control of motile ciliogenesis |
| title_sort | cyclin dependent kinase control of motile ciliogenesis |
| topic | cilia ciliogenesis centriole cell cycle Cdk2 Cyclin A1 |
| url | https://elifesciences.org/articles/36375 |
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