ADF and Cofilin1 control actin stress fibers, nuclear integrity, and cell survival

Kanellos, G. et al. (2015) ADF and Cofilin1 control actin stress fibers, nuclear integrity, and cell survival. Cell Reports, 13(9), pp. 1949-1964. (doi: 10.1016/j.celrep.2015.10.056) (PMID:26655907) (PMCID:PMC4678118)

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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.

Item Type:Articles
Additional Information:This work was funded by Cancer Research UK (CRUK) Program Grant to M.C.F. and V.G.B. (no. C157/A15703) and European Research Council Advanced Investigator grant to M.C.F. (no. 294440 Cancer Innovation; supporting H.P.). It was also supported by CRUK China Fellowship to J.Z. (no. C157/A11682), by CRUK PhD studentship to G.K., by CRUK Beatson core program to O.J.S., and by AICR grant to M.C.F. (no. 09-0316) that funded H.P.
Glasgow Author(s) Enlighten ID:Frame, Prof Margaret and Ridgway, Dr Rachel and Brunton, Dr Valerie and Sandilands, Dr Emma and Sansom, Professor Owen
Authors: Kanellos, G., Zhou, J., Patel, H., Ridgway, R. A., Huels, D., Gurniak, C. B., Sandilands, E., Carragher, N. O., Sansom, O. J., Witke, W., Brunton, V. G., and Frame, M. C.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cell Reports
ISSN (Online):2211-1247
Published Online:19 November 2015
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Cell Reports 13(9):1949-1964
Publisher Policy:Reproduced under a Creative Commons license

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