Hetmanski, J. H.R. et al. (2019) Membrane tension orchestrates rear retraction in matrix directed cell migration. Developmental Cell, 51(4), 460-475.e10. (doi: 10.1016/j.devcel.2019.09.006) (PMID:31607653) (PMCID:PMC6863396)
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Abstract
In development, wound healing, and cancer metastasis, vertebrate cells move through 3D interstitial matrix, responding to chemical and physical guidance cues. Protrusion at the cell front has been extensively studied, but the retraction phase of the migration cycle is not well understood. Here, we show that fast-moving cells guided by matrix cues establish positive feedback control of rear retraction by sensing membrane tension. We reveal a mechanism of rear retraction in 3D matrix and durotaxis controlled by caveolae, which form in response to low membrane tension at the cell rear. Caveolae activate RhoA-ROCK1/PKN2 signaling via the RhoA guanidine nucleotide exchange factor (GEF) Ect2 to control local F-actin organization and contractility in this subcellular region and promote translocation of the cell rear. A positive feedback loop between cytoskeletal signaling and membrane tension leads to rapid retraction to complete the migration cycle in fast-moving cells, providing directional memory to drive persistent cell migration in complex matrices.
Item Type: | Articles |
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Additional Information: | The Bioimaging Facility microscopes were purchased with grants from BBSRC, Wellcome, and the University of Manchester Strategic Fund (UK). The Liverpool Centre for Cell Imaging (CCI) provided access to equipment (BBSRC grant BB/M012441/1). P.T.C. is supported by the MRC (MR/R009376/1), J.S. is supported by the BBSRC (BB/ L024551/1), and the Wellcome Trust Centre for Cell-Matrix Research is funded by grant 203128/Z/16/Z. CLEM experiments were funded by ARC (Programme labellise´ to J.G.G.) and by institutional funds from INSERM and University of Strasbourg (France). I.B. is supported by ARC (Programme labellise´ to J.G.G.), and we are grateful to Luc Mercier for help with the CLEM approach and Cathy Royer (INCI, Strasbourg) for access to TEM. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Dobre, Dr Oana |
Authors: | Hetmanski, J. H.R., de Belly, H., Nair, R. V., Sokleva, V., Dobre, O., Cameron, A., Gauthier, N., Lamaze, C., Swift, J., del Campo, A., Paluch, E., Schwartz, J.-M., and Caswell, P. |
College/School: | College of Science and Engineering > School of Engineering > Biomedical Engineering |
Journal Name: | Developmental Cell |
Publisher: | Elsevier (Cell Press) |
ISSN: | 1534-5807 |
ISSN (Online): | 1878-1551 |
Published Online: | 10 October 2019 |
Copyright Holders: | Copyright © 2019 The Authors |
First Published: | First published in Developmental Cell 51(4): 460-475.e10 |
Publisher Policy: | Reproduced under a Creative Commons License |
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