Galvanin (TMEM154) is a conserved single-pass transmembrane protein that functions as a direct electric field sensor for directed cell migration by rapidly relocalizing to the anodal cell pole through electrophoresis of its negatively charged ectodomain and transducing spatial information via its intracellular domain to reorient cellular protrusion and retraction machinery, with its expression being both necessary across multiple immune and epithelial cell types and sufficient to confer cathodal electrotaxis on otherwise non-responsive cells.

Directed cell migration of immune and epithelial cells is critical for their rapid response to tissue injury or infection. Endogenous electric fields generated by disruption of the transepithelial potential across the skin have been postulated to play an important role in guiding cells to wound sites, though how individual cells sense these tissue-scale physical cues remains largely unknown. We have identified Galvanin (TMEM154), a previously uncharacterized single-pass transmembrane protein, as being required for electric-field-guided migration of individual rapidly moving cells. Galvanin functions in both immune and epithelial cell types. Upon exposure of cells to an electric field, Galvanin rapidly relocalizes to the anodal side of a cell, and the net charge on its extracellular domain is necessary and sufficient to drive this spatial relocalization. Furthermore, expression of Galvanin is sufficient to confer electric field–guided migration on otherwise non-responsive epithelial cells. In human neutrophils, we show that Galvanin relocalization is immediately followed by changes in the spatial pattern of cellular protrusion and retraction. The strong directional response of these cells is lost upon truncation of Galvanin’s intracellular domain, suggesting that Galvanin acts as a direct sensor of the electric field, transducing spatial information about a cell’s electrical environment to the intracellular migratory apparatus. This sensor relocalization mechanism of cell steering defines a new paradigm for directed cell migration.