Gβ Regulates Coupling between Actin Oscillators for Cell Polarity and Directional Migration

Oliver Hoeller, Jared E. Toettcher, Huaqing Cai, Yaohui Sun, Chuan Hsiang Huang, Mariel Freyre, Min Zhao, Peter N. Devreotes, Orion D. Weiner

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

For directional movement, eukaryotic cells depend on the proper organization of their actin cytoskeleton. This engine of motility is made up of highly dynamic nonequilibrium actin structures such as flashes, oscillations, and traveling waves. In Dictyostelium, oscillatory actin foci interact with signals such as Ras and phosphatidylinositol 3,4,5-trisphosphate (PIP3) to form protrusions. However, how signaling cues tame actin dynamics to produce a pseudopod and guide cellular motility is a critical open question in eukaryotic chemotaxis. Here, we demonstrate that the strength of coupling between individual actin oscillators controls cell polarization and directional movement. We implement an inducible sequestration system to inactivate the heterotrimeric G protein subunit Gβ and find that this acute perturbation triggers persistent, high-amplitude cortical oscillations of F-actin. Actin oscillators that are normally weakly coupled to one another in wild-type cells become strongly synchronized following acute inactivation of Gβ. This global coupling impairs sensing of internal cues during spontaneous polarization and sensing of external cues during directional motility. A simple mathematical model of coupled actin oscillators reveals the importance of appropriate coupling strength for chemotaxis: moderate coupling can increase sensitivity to noisy inputs. Taken together, our data suggest that Gβ regulates the strength of coupling between actin oscillators for efficient polarity and directional migration. As these observations are only possible following acute inhibition of Gβ and are masked by slow compensation in genetic knockouts, our work also shows that acute loss-of-function approaches can complement and extend the reach of classical genetics in Dictyostelium and likely other systems as well.

Original languageEnglish (US)
Article numbere1002381
JournalPLoS Biology
Volume14
Issue number2
DOIs
StatePublished - Feb 18 2016

Fingerprint

Cell Polarity
actin
Actins
strength (mechanics)
Cues
Dictyostelium
chemotaxis
Chemotaxis
oscillation
pseudopodia
Heterotrimeric GTP-Binding Proteins
Polarization
Pseudopodia
cell polarity
phosphatidylinositols
Protein Subunits
Eukaryotic Cells
protein subunits
engines
microfilaments

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Hoeller, O., Toettcher, J. E., Cai, H., Sun, Y., Huang, C. H., Freyre, M., ... Weiner, O. D. (2016). Gβ Regulates Coupling between Actin Oscillators for Cell Polarity and Directional Migration. PLoS Biology, 14(2), [e1002381]. https://doi.org/10.1371/journal.pbio.1002381

Gβ Regulates Coupling between Actin Oscillators for Cell Polarity and Directional Migration. / Hoeller, Oliver; Toettcher, Jared E.; Cai, Huaqing; Sun, Yaohui; Huang, Chuan Hsiang; Freyre, Mariel; Zhao, Min; Devreotes, Peter N.; Weiner, Orion D.

In: PLoS Biology, Vol. 14, No. 2, e1002381, 18.02.2016.

Research output: Contribution to journalArticle

Hoeller, O, Toettcher, JE, Cai, H, Sun, Y, Huang, CH, Freyre, M, Zhao, M, Devreotes, PN & Weiner, OD 2016, 'Gβ Regulates Coupling between Actin Oscillators for Cell Polarity and Directional Migration', PLoS Biology, vol. 14, no. 2, e1002381. https://doi.org/10.1371/journal.pbio.1002381
Hoeller, Oliver ; Toettcher, Jared E. ; Cai, Huaqing ; Sun, Yaohui ; Huang, Chuan Hsiang ; Freyre, Mariel ; Zhao, Min ; Devreotes, Peter N. ; Weiner, Orion D. / Gβ Regulates Coupling between Actin Oscillators for Cell Polarity and Directional Migration. In: PLoS Biology. 2016 ; Vol. 14, No. 2.
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