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Title: β4 Integrin and Epidermal Growth Factor Coordinately Regulate Electric Field-mediated Directional Migration via Rac1
Authors: Pullar, Christine E.
Baier, Brian S.
Kariya, Yoshinobu
Russell, Alan J.
Horst, Basil A.J.
Marinkovich, M. Peter
Isseroff, R. Rivkah
First Published: 16-Aug-2006
Publisher: American society for cell biology
Citation: Molecular biology of the cell, 2006, 17 (11), pp.4925-4935
Abstract: Endogenous DC electric fields (EF) are present during embryogenesis and are generated in vivo upon wounding, providing guidance cues for directional cell migration (galvanotaxis) required in these processes. To understand the role of beta (β)4 integrin in directional migration, the migratory paths of either primary human keratinocytes (NHK), β4 integrin-null human keratinocytes (β4−), or those in which β4 integrin was reexpressed (β4+), were tracked during exposure to EFs of physiological magnitude (100 mV/mm). Although the expression of β4 integrin had no effect on the rate of cell movement, it was essential for directional (cathodal) migration in the absence of epidermal growth factor (EGF). The addition of EGF potentiated the directional response, suggesting that at least two distinct but synergistic signaling pathways coordinate galvanotaxis. Expression of either a ligand binding–defective β4 (β4+AD) or β4 with a truncated cytoplasmic tail (β4+CT) resulted in loss of directionality in the absence of EGF, whereas inhibition of Rac1 blinded the cells to the EF even in the presence of EGF. In summary, both the β4 integrin ligand–binding and cytoplasmic domains together with EGF were required for the synergistic activation of a Rac-dependent signaling pathway that was essential for keratinocyte directional migration in response to a galvanotactic stimulus.
DOI Link: 10.1091/mbc.E06-05-0433
ISSN: 1059-1524
eISSN: 1939-4586
Version: Publisher Version
Status: Peer-reviewed
Type: Article
Rights: Copyright © the authors, 2006. This is an open-access article distributed under the terms of the Creative Commons Attribution-ShareAlike Licence (
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

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