Spatio-Temporal Regulation of Rac1 Mobility by Actin Islands

Rho GTPases play important roles in many aspects of cell migration, including polarity establishment and organizing actin cytoskeleton. In particular, the Rho GTPase Rac1 has been associated with the generation of protrusions at leading edge of migrating cells. Previously we showed the mobility of R...

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Bibliographic Details
Published in:PloS one 2015-11, Vol.10 (11), p.e0143753-e0143753
Main Authors: Lakhani, Vinal V, Hinde, Elizabeth, Gratton, Enrico, Elston, Timothy C
Format: Article
Language:English
Subjects:
Actin
Actin Cytoskeleton - metabolism
Actins - metabolism
Algorithms
Analysis
Bioinformatics
Biology
Biophysics
Biosensing Techniques
Biosensors
Cell migration
Computer Simulation
Curricula
Cytoskeleton
Diffusion
Experiments
Guanosine triphosphatases
Guanosinetriphosphatase
Hypotheses
Intracellular Space - metabolism
Islands
Localization
Mobility
Models, Biological
Muscle proteins
Physiological aspects
Polarity
Protein Binding
Protein Transport
rac1 GTP-Binding Protein - metabolism
Rac1 protein
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Summary:Rho GTPases play important roles in many aspects of cell migration, including polarity establishment and organizing actin cytoskeleton. In particular, the Rho GTPase Rac1 has been associated with the generation of protrusions at leading edge of migrating cells. Previously we showed the mobility of Rac1 molecules is not uniform throughout a migrating cell (Hinde E et. al. PNAS 2013). Specifically, the closer a Rac1 molecule is to the leading edge, the slower the molecule diffuses. Because actin-bound Rac1 diffuses slower than unbound Rac1, we hypothesized that regions of high actin concentration, called "actin islands", act as diffusive traps and are responsible for the non-uniform diffusion observed in vivo. Here, in silico model simulations demonstrate that equally spaced actin islands can regulate the time scale for Rac1 diffusion in a manner consistent with data from live-cell imaging experiments. Additionally, we find this mechanism is robust; different patterns of Rac1 mobility can be achieved by changing the actin islands' positions or their affinity for Rac1.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0143753