Editors' ChoiceGalvanotaxis

Electrical Orienteering

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Sci. Signal.  16 Apr 2013:
Vol. 6, Issue 271, pp. ec89
DOI: 10.1126/scisignal.2004247

Many motile cells exhibit galvanotaxis (directional migration in response to an electric field) and can respond to currents as weak as those found in intact epithelia. In addition to being characterized in slime molds and protozoa, galvanotaxis has also been implicated in epithelial wound healing and embryonic development in metazoans. Some of the signaling components required for galvanotaxis are shared with chemotaxis, but how cells sense electrical fields is unclear. Allen et al. investigated some of the proposed mechanisms for electric field sensing in zebrafish keratocytes. Ion current through the plasma membrane was not required, because keratocytes placed in an electric field migrated toward the cathode even in the absence of extracellular Na+, K+, or Ca2+ or in the presence of a Ca2+ ionophore, an intracellular Ca2+ chelator, an L-type Ca2+ channel inhibitor, a Na+/H+ exchanger inhibitor, or a volume-regulated anion channel inhibitor. Although galvanotaxing cells reoriented in response to shear stress imposed by laminar fluid flow, electro-osmotic fluid flow (the flow across a material initiated by an applied electric current) at the migration substrate was not sufficient to reorient galvanotaxing cells. Changing the aqueous viscosity of the culture medium increased the time it took for cells to respond to an electric field and to reset their polarization upon reversal of the electric field, consistent with a model in which electrophoretic motion of charged membrane components toward the anode was important for sensing the field. A fluorescently labeled lectin (Concavalin A) redistributed to the anode-facing side of cells on a time scale compatible with repolarization time. Experiments with varying extracellular pH suggested that protonation of membrane components could cause galvanotaxis failure, which is consistent with the electrophoretic model. The authors propose a model in which polarization of cell membrane components induced by an electric field causes asymmetric activation of intracellular signaling pathways. In a related study, Sun et al. investigated the intracellular mechanisms determining directionality in galvanotaxis. Whereas keratocytes migrated toward the cathode, the anuclear cell fragments that spontaneously detach from them migrated toward the anode. Inhibiting phosphoinositide 3-kinase (PI3K), which relays signals to the actin cytoskeleton at the forward edge of migrating cells, reversed the direction of keratocyte migration but had no effect on the direction in which keratocyte fragments migrated. Conversely, disrupting the myosin dynamics that define the rear of migrating cells interfered with anode-directed migration of cell fragments but not with cathode-directed migration of keratocytes. Inhibiting PI3K and myosin dynamics simultaneously abolished directional migration in both keratocytes and keratocyte fragments. The authors hypothesize that the PI3K and myosin systems define the front and rear of a cell, respectively, and compete to determine the direction of migration in an electric field. Although it is not clear why the PI3K pathway dominates in whole keratocytes and the myosin pathway dominates in keratocyte fragments, these findings point to a model in which cells use actomyosin contractile networks as a compass to orient themselves in an electric field.

G. M. Allen, A. Mogilner, J. A. Theriot, Electrophoresis of cellular membrane components creates the directional cue guiding keratocyte galvanotaxis. Curr. Biol. 23, 560–588 (2013). [PubMed]

Y. Sun, H. Do, J. Gao, R. Zhao, M. Zhao, A. Mogilner, Keratocyte fragments and cells utilize competing pathways to move in opposite directions in an electric field. Curr. Biol. 23, 569–574 (2013). [PubMed]

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