Principles that govern competition or co-existence in Rho-GTPase driven polarization

Rho-GTPases are master regulators of polarity establishment and cell morphology. Positive feedback enables concentration of Rho-GTPases into clusters at the cell cortex, from where they regulate the cytoskeleton. Different cell types reproducibly generate either one (e.g. the front of a migrating ce...

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Bibliographic Details
Published in:PLoS computational biology 2018-04, Vol.14 (4), p.e1006095-e1006095
Main Authors: Chiou, Jian-Geng, Ramirez, Samuel A, Elston, Timothy C, Witelski, Thomas P, Schaeffer, David G, Lew, Daniel J
Format: Article
Language:English
Subjects:
Applied mathematics
Biology
Biology and Life Sciences
Cell morphology
Circuit design
Clusters
Coexistence
Competition
Cytology
Cytoskeleton
Dendrites
Feedback
GTPases
Guanine nucleotide-binding protein
Guanosine triphosphatases
Health aspects
Mathematical models
Morphology
Parameters
Pharmacology
Physical Sciences
Polarity
Positive feedback
Regulators
Research and Analysis Methods
Saturation
Theory
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Summary:Rho-GTPases are master regulators of polarity establishment and cell morphology. Positive feedback enables concentration of Rho-GTPases into clusters at the cell cortex, from where they regulate the cytoskeleton. Different cell types reproducibly generate either one (e.g. the front of a migrating cell) or several clusters (e.g. the multiple dendrites of a neuron), but the mechanistic basis for unipolar or multipolar outcomes is unclear. The design principles of Rho-GTPase circuits are captured by two-component reaction-diffusion models based on conserved aspects of Rho-GTPase biochemistry. Some such models display rapid winner-takes-all competition between clusters, yielding a unipolar outcome. Other models allow prolonged co-existence of clusters. We investigate the behavior of a simple class of models and show that while the timescale of competition varies enormously depending on model parameters, a single factor explains a large majority of this variation. The dominant factor concerns the degree to which the maximal active GTPase concentration in a cluster approaches a "saturation point" determined by model parameters. We suggest that both saturation and the effect of saturation on competition reflect fundamental properties of the Rho-GTPase polarity machinery, regardless of the specific feedback mechanism, which predict whether the system will generate unipolar or multipolar outcomes.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1006095