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J Cell Biol. 2017 Dec 4;216(12):4271-4285. doi: 10.1083/jcb.201706052. Epub 2017 Oct 20.

An excitable Rho GTPase signaling network generates dynamic subcellular contraction patterns.

Author information

1
Department of Molecular Cell Biology, Center for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.
2
Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology and Fakultät für Chemie und Chemische Biologie, TU Dortmund University, Dortmund, Germany.
3
Institute of Complex Systems, Forschungszentrum Jülich, Jülich, Germany.
4
Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology and Fakultät für Chemie und Chemische Biologie, TU Dortmund University, Dortmund, Germany leif.dehmelt@mpi-dortmund.mpg.de.
5
Department of Molecular Cell Biology, Center for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany perihan.nalbant@uni-due.de.

Abstract

Rho GTPase-based signaling networks control cellular dynamics by coordinating protrusions and retractions in space and time. Here, we reveal a signaling network that generates pulses and propagating waves of cell contractions. These dynamic patterns emerge via self-organization from an activator-inhibitor network, in which the small GTPase Rho amplifies its activity by recruiting its activator, the guanine nucleotide exchange factor GEF-H1. Rho also inhibits itself by local recruitment of actomyosin and the associated RhoGAP Myo9b. This network structure enables spontaneous, self-limiting patterns of subcellular contractility that can explore mechanical cues in the extracellular environment. Indeed, actomyosin pulse frequency in cells is altered by matrix elasticity, showing that coupling of contractility pulses to environmental deformations modulates network dynamics. Thus, our study reveals a mechanism that integrates intracellular biochemical and extracellular mechanical signals into subcellular activity patterns to control cellular contractility dynamics.

PMID:
29055010
PMCID:
PMC5716289
DOI:
10.1083/jcb.201706052
[Indexed for MEDLINE]
Free PMC Article

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