Force-induced cell polarisation is linked to RhoA-driven microtubule-independent focal-adhesion sliding
Open Access
- 15 October 2009
- journal article
- research article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 122 (20), 3644-3651
- https://doi.org/10.1242/jcs.054866
Abstract
Mechanical forces play a crucial role in controlling the integrity and functionality of cells and tissues. External forces are sensed by cells and translated into signals that induce various responses. To increase the detailed understanding of these processes, we investigated cell migration and dynamic cellular reorganisation of focal adhesions and cytoskeleton upon application of cyclic stretching forces. Of particular interest was the role of microtubules and GTPase activation in the course of mechanotransduction. We showed that focal adhesions and the actin cytoskeleton undergo dramatic reorganisation perpendicular to the direction of stretching forces even without microtubules. Rather, we found that microtubule orientation is controlled by the actin cytoskeleton. Using biochemical assays and fluorescence resonance energy transfer (FRET) measurements, we revealed that Rac1 and Cdc42 activities did not change upon stretching, whereas overall RhoA activity increased dramatically, but independently of intact microtubules. In conclusion, we demonstrated that key players in force-induced cellular reorganisation are focal-adhesion sliding, RhoA activation and the actomyosin machinery. In contrast to the importance of microtubules in migration, the force-induced cellular reorganisation, including focal-adhesion sliding, is independent of a dynamic microtubule network. Consequently, the elementary molecular mechanism of cellular reorganisation during migration is different to the one in force-induced cell reorganisation.Keywords
This publication has 49 references indexed in Scilit:
- Focal adhesion kinase: switching between GAPs and GEFs in the regulation of cell motilityCurrent Opinion in Cell Biology, 2009
- Two Characteristic Regimes in Frequency-Dependent Dynamic Reorientation of Fibroblasts on Cyclically Stretched SubstratesBiophysical Journal, 2008
- FAK, PDZ-RhoGEF and ROCKII cooperate to regulate adhesion movement and trailing-edge retraction in fibroblastsJournal of Cell Science, 2008
- PyK2 and FAK connections to p190Rho guanine nucleotide exchange factor regulate RhoA activity, focal adhesion formation, and cell motilityThe Journal of cell biology, 2008
- Vinculin controls focal adhesion formation by direct interactions with talin and actinThe Journal of cell biology, 2007
- Mechanoregulation of gene expression in fibroblastsGene, 2007
- Rac1 activity is required for cardiac myocyte alignment in response to mechanical stressBiochemical and Biophysical Research Communications, 2007
- Mechanical force mobilizes zyxin from focal adhesions to actin filaments and regulates cytoskeletal reinforcementThe Journal of cell biology, 2005
- Elastic properties of nematoid arrangements formed by amoeboid cellsThe European Physical Journal E, 2000
- Microtubule Targeting of Substrate Contacts Promotes Their Relaxation and DissociationThe Journal of cell biology, 1999