ADF and Cofilin1 Control Actin Stress Fibers, Nuclear Integrity, and Cell Survival
Genetic co-depletion of the actin-severing proteins ADF and CFL1 triggers catastrophic loss of adult homeostasis in multiple tissues. There is impaired cell-cell adhesion in skin keratinocytes with dysregulation of E-cadherin, hyperproliferation of differentiated cells, and ultimately apoptosis. Mec...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715012450 |
| _version_ | 1819264369877319680 |
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| author | Georgios Kanellos Jing Zhou Hitesh Patel Rachel A. Ridgway David Huels Christine B. Gurniak Emma Sandilands Neil O. Carragher Owen J. Sansom Walter Witke Valerie G. Brunton Margaret C. Frame |
| author_facet | Georgios Kanellos Jing Zhou Hitesh Patel Rachel A. Ridgway David Huels Christine B. Gurniak Emma Sandilands Neil O. Carragher Owen J. Sansom Walter Witke Valerie G. Brunton Margaret C. Frame |
| author_sort | Georgios Kanellos |
| collection | DOAJ |
| description | Genetic co-depletion of the actin-severing proteins ADF and CFL1 triggers catastrophic loss of adult homeostasis in multiple tissues. There is impaired cell-cell adhesion in skin keratinocytes with dysregulation of E-cadherin, hyperproliferation of differentiated cells, and ultimately apoptosis. Mechanistically, the primary consequence of depleting both ADF and CFL1 is uncontrolled accumulation of contractile actin stress fibers associated with enlarged focal adhesions at the plasma membrane, as well as reduced rates of membrane protrusions. This generates increased intracellular acto-myosin tension that promotes nuclear deformation and physical disruption of the nuclear lamina via the LINC complex that normally connects regulated actin filaments to the nuclear envelope. We therefore describe a pathway involving the actin-severing proteins ADF and CFL1 in regulating the dynamic turnover of contractile actin stress fibers, and this is vital to prevent the nucleus from being damaged by actin contractility, in turn preserving cell survival and tissue homeostasis. |
| first_indexed | 2024-12-23T20:28:24Z |
| format | Article |
| id | doaj.art-68d74766f9794e91b13d8444278d7b47 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-23T20:28:24Z |
| publishDate | 2015-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-68d74766f9794e91b13d8444278d7b472022-12-21T17:32:18ZengElsevierCell Reports2211-12472015-12-011391949196410.1016/j.celrep.2015.10.056ADF and Cofilin1 Control Actin Stress Fibers, Nuclear Integrity, and Cell SurvivalGeorgios Kanellos0Jing Zhou1Hitesh Patel2Rachel A. Ridgway3David Huels4Christine B. Gurniak5Emma Sandilands6Neil O. Carragher7Owen J. Sansom8Walter Witke9Valerie G. Brunton10Margaret C. Frame11Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UKEdinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UKEdinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UKCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UKCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UKInstitute of Genetics, University of Bonn, Karlrobert-Kreiten Strasse 13, 53115 Bonn, GermanyEdinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UKEdinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UKCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UKInstitute of Genetics, University of Bonn, Karlrobert-Kreiten Strasse 13, 53115 Bonn, GermanyEdinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UKEdinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UKGenetic co-depletion of the actin-severing proteins ADF and CFL1 triggers catastrophic loss of adult homeostasis in multiple tissues. There is impaired cell-cell adhesion in skin keratinocytes with dysregulation of E-cadherin, hyperproliferation of differentiated cells, and ultimately apoptosis. Mechanistically, the primary consequence of depleting both ADF and CFL1 is uncontrolled accumulation of contractile actin stress fibers associated with enlarged focal adhesions at the plasma membrane, as well as reduced rates of membrane protrusions. This generates increased intracellular acto-myosin tension that promotes nuclear deformation and physical disruption of the nuclear lamina via the LINC complex that normally connects regulated actin filaments to the nuclear envelope. We therefore describe a pathway involving the actin-severing proteins ADF and CFL1 in regulating the dynamic turnover of contractile actin stress fibers, and this is vital to prevent the nucleus from being damaged by actin contractility, in turn preserving cell survival and tissue homeostasis.http://www.sciencedirect.com/science/article/pii/S2211124715012450 |
| spellingShingle | Georgios Kanellos Jing Zhou Hitesh Patel Rachel A. Ridgway David Huels Christine B. Gurniak Emma Sandilands Neil O. Carragher Owen J. Sansom Walter Witke Valerie G. Brunton Margaret C. Frame ADF and Cofilin1 Control Actin Stress Fibers, Nuclear Integrity, and Cell Survival Cell Reports |
| title | ADF and Cofilin1 Control Actin Stress Fibers, Nuclear Integrity, and Cell Survival |
| title_full | ADF and Cofilin1 Control Actin Stress Fibers, Nuclear Integrity, and Cell Survival |
| title_fullStr | ADF and Cofilin1 Control Actin Stress Fibers, Nuclear Integrity, and Cell Survival |
| title_full_unstemmed | ADF and Cofilin1 Control Actin Stress Fibers, Nuclear Integrity, and Cell Survival |
| title_short | ADF and Cofilin1 Control Actin Stress Fibers, Nuclear Integrity, and Cell Survival |
| title_sort | adf and cofilin1 control actin stress fibers nuclear integrity and cell survival |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715012450 |
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