title: Gβ Regulates Coupling between Actin Oscillators for Cell Polarity and Directional Migration.
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.
authors.affiliation: Cardiovascular Research Institute and Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hoeller
authors.affiliation: Cardiovascular Research Institute and Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Jared E
authors.initials: JE
authors.lastname: Toettcher
authors.affiliation: Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Huaqing
authors.initials: H
authors.lastname: Cai
authors.affiliation: Institute for Regenerative Cures, Department of Dermatology, University of California Davis School of Medicine, Sacramento, California, United States of America.
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Chuan-Hsiang
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Swarthmore College, Swarthmore, Pennsylvania, United States of America.
authors.forename: Mariel
authors.initials: M
authors.lastname: Freyre
authors.affiliation: Institute for Regenerative Cures, Department of Dermatology, University of California Davis School of Medicine, Sacramento, California, United States of America.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Devreotes
authors.affiliation: Cardiovascular Research Institute and Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Orion D
authors.initials: OD
authors.lastname: Weiner
mesh_terms: D000199:Actins / Q000378:metabolism*; D001683:Biological Clocks; D002465:Cell Movement; D016764:Cell Polarity; D003599:Cytoskeleton / Q000378:metabolism; D004023:Dictyostelium; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism*; D008954:Models, Biological; D015398:Signal Transduction; D020123:Sirolimus
chemical_list: D000199:Actins; D044387:GTP-Binding Protein beta Subunits; D020123:Sirolimus