Galvanin (TMEM154) is an electric-field sensor for directed cell migration

Area of Science:

• Cell biology
• Biophysics
• Immunology

Background:

• Directed cell migration is crucial for immune responses to injury and infection.
• Endogenous electric fields guide immune and skin cells to wound sites.
• The precise mechanisms of cellular electrotaxis remain largely unknown.

Purpose of the Study:

• To identify the molecular mechanisms by which neutrophils sense and respond to electric fields.
• To characterize the role of newly identified proteins in directed cell migration.

Main Methods:

• Utilized a CRISPR-based genetic screen to identify key proteins involved in neutrophil electrotaxis.
• Investigated the localization and function of the identified protein, Galvanin, using live-cell imaging and electrophysiological techniques.

Main Results:

• Identified Galvanin, a novel single-pass transmembrane protein, as essential for human neutrophil directional change in response to electric fields.
• Demonstrated that Galvanin rapidly relocalizes to the anodal side of neutrophils upon electric field exposure.
• Showed that the net charge of Galvanin's extracellular domain drives its electric field-induced relocalization and subsequent changes in cell protrusion and retraction patterns.

Conclusions:

• Galvanin acts as a direct sensor of electric fields, translating electrical environmental cues into directed cell migration.
• This sensor relocalization mechanism represents a new paradigm for directed cell migration, particularly in immune cell responses.
• Understanding Galvanin's function opens new avenues for modulating immune cell trafficking and wound healing.