Abstract
BackgroundCells show directed migration response to electric signals, namely electrotaxis or galvanotaxis. PI3K and PTEN jointly play counterbalancing roles in this event via a bilateral regulation of PIP3 signaling. PI3K has been proved essential in anterior signaling of electrotaxing cells, whilst the role of PTEN remains elusive.MethodsDictyostelium cells with different genetic backgrounds were treated with direct current electric signals to investigate the genetic regulation of electrotaxis.ResultsWe demonstrated that electric signals promoted PTEN phosphatase activity and asymmetrical translocation to the posterior plasma membrane of the electrotaxing cells. Electric stimulation produced a similar but delayed rear redistribution of myosin II, immediately before electrotaxis started. Actin polymerization is required for the asymmetric membrane translocation of PTEN and myosin. PTEN signaling is also responsible for the asymmetric anterior redistribution of PIP3/F-actin, and a biased redistribution of pseudopod protrusion in the forwarding direction of electrotaxing cells.ConclusionsPTEN controls electrotaxis by coordinately regulating asymmetric redistribution of myosin to the posterior, and PIP3/F-actin to the anterior region of the directed migration cells.
Highlights
Physiological electric signals function as one of the vital guidance cues for directed cell migration during wound healing, development and regeneration of multicellular organisms
PTEN is required in the electrotactic response of Dictyostelium In the absence of electric fields (EFs), AX2 wild type (WT) cells moved randomly with the migration directedness close to zero
Red lines and blue arrows are cell trajectories and endpoints over 15 min. d-f Composite trajectories of migrating cells with the starting points placed at the origin. b and e pten− cells showed significantly reduced electrotaxis. c and f The re-expression of wild type pten on pten− (PTEN/pten−, or pten rescue) completely reversed the electrotaxis defects in the pten− cells. g, h voltage dependence migration directedness and trajectory speed. *, P < 0.05; **, P < 0.01, compared with no EF control; #, P < 0.05; ##, P < 0.01 compared between WT/pten rescue groups and pten− group, one-way analysis of variance (ANOVA)
Summary
Physiological electric signals function as one of the vital guidance cues for directed cell migration during wound healing, development and regeneration of multicellular organisms. Many cell types have shown directed cell migration response to applied electric fields (EFs), namely electrotaxis or galvanotaxis [1,2,3,4,5,6,7,8,9]. Our previous studies proved that EF could drive a variety of growth factor receptors and membrane lipids to redistribute asymmetrically, leading to polarized PI3K vs PTEN signaling in electrotaxing cells [1, 4, 8, 9]. Asymmetric PI3K redistribution to the leading edge of the cells has been shown to play an important role in the control of electrotaxis [9]; the mechanistic regulation of PTEN in electrotaxis remains elusive. Cells show directed migration response to electric signals, namely electrotaxis or galvanotaxis. PI3K has been proved essential in anterior signaling of electrotaxing cells, whilst the role of PTEN remains elusive
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